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  • Binding Sites  (115)
  • American Association for the Advancement of Science (AAAS)  (115)
  • American Association of Petroleum Geologists (AAPG)
  • Elsevier
  • 1990-1994  (115)
  • 1975-1979
  • 1992  (66)
  • 1990  (49)
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  • American Association for the Advancement of Science (AAAS)  (115)
  • American Association of Petroleum Geologists (AAPG)
  • Elsevier
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  • 1990-1994  (115)
  • 1975-1979
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  • 1
    Publication Date: 1992-11-13
    Description: When glycine418 of Escherichia coli glutathione reductase, which is in a closely packed region of the dimer interface, is replaced with a bulky tryptophan residue, the enzyme becomes highly cooperative (Hill coefficient 1.76) for glutathione binding. The cooperativity is lost when the mutant subunit is hybridized with a wild-type subunit to create a heterodimer. The mutation appears to disrupt atomic packing at the dimer interface, which induces a change of kinetic mechanism. A single mutation in a region of the protein remote from the active site can thus act as a molecular switch to confer cooperativity on an enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scrutton, N S -- Deonarain, M P -- Berry, A -- Perham, R N -- New York, N.Y. -- Science. 1992 Nov 13;258(5085):1140-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Cambridge, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1439821" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Escherichia coli/*enzymology/genetics ; Genes, Bacterial ; Glutathione/metabolism ; Glutathione Reductase/*chemistry/genetics/metabolism ; Glycine/chemistry ; Kinetics ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; *Mutagenesis, Site-Directed ; NADP/metabolism ; Plasmids ; Protein Multimerization ; Tryptophan/chemistry
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-03-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abelson, J -- New York, N.Y. -- Science. 1992 Mar 13;255(5050):1390.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena 91125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1542787" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Endoribonucleases/*metabolism ; Introns/*physiology ; RNA Precursors/*metabolism ; RNA Splicing/*physiology ; RNA, Transfer/*metabolism
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  • 3
    Publication Date: 1992-07-31
    Description: The Wilms tumor suppressor gene wt1 encodes a zinc finger DNA binding protein, WT1, that functions as a transcriptional repressor. The fetal mitogen insulin-like growth factor II (IGF-II) is overexpressed in Wilms tumors and may have autocrine effects in tumor progression. The major fetal IGF-II promoter was defined in transient transfection assays as a region spanning from nucleotides -295 to +135, relative to the transcription start site. WT1 bound to multiple sites in this region and functioned as a potent repressor of IGF-II transcription in vivo. Maximal repression was dependent on the presence of WT1 binding sites on each side of the transcriptional initiation site. These findings provide a molecular basis for overexpression of IGF-II in Wilms tumors and suggest that WT1 negatively regulates blastemal cell proliferation by limiting the production of a fetal growth factor in the developing vertebrate kidney.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Drummond, I A -- Madden, S L -- Rohwer-Nutter, P -- Bell, G I -- Sukhatme, V P -- Rauscher, F J 3rd -- CA 10817/CA/NCI NIH HHS/ -- CA 47983/CA/NCI NIH HHS/ -- CA 52009/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Jul 31;257(5070):674-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Chicago, IL 60637.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1323141" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Blotting, Northern ; DNA/chemistry/metabolism ; DNA-Binding Proteins/*metabolism ; Deoxyribonuclease I/metabolism ; *Gene Expression Regulation, Neoplastic ; Genes, Wilms Tumor/*physiology ; Humans ; Insulin-Like Growth Factor II/*genetics ; Kidney/embryology/metabolism ; Mice ; Molecular Sequence Data ; Promoter Regions, Genetic ; Rats ; Sequence Homology, Nucleic Acid ; Transfection ; WT1 Proteins ; Wilms Tumor/genetics/metabolism ; Zinc Fingers
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  • 4
    Publication Date: 1992-09-25
    Description: Two major developmentally regulated isoforms of the Drosophila chorion transcription factor CF2 differ by an extra zinc finger within the DNA binding domain. The preferred DNA binding sites were determined and are distinguished by an internal duplication of TAT in the site recognized by the isoform with the extra finger. The results are consistent with modular interactions between zinc fingers and trinucleotides and also suggest rules for recognition of AT-rich DNA sites by zinc finger proteins. The results show how modular finger interactions with trinucleotides can be used, in conjunction with alternative splicing, to alter the binding specificity and increase the spectrum of sites recognized by a DNA binding domain. Thus, CF2 may potentially regulate distinct sets of target genes during development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gogos, J A -- Hsu, T -- Bolton, J -- Kafatos, F C -- New York, N.Y. -- Science. 1992 Sep 25;257(5078):1951-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Developmental Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1290524" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; DNA-Binding Proteins/*metabolism ; *Drosophila Proteins ; Drosophila melanogaster/genetics ; Hydrogen Bonding ; Molecular Sequence Data ; Oligodeoxyribonucleotides/chemistry/metabolism ; Protein Binding ; *Regulatory Sequences, Nucleic Acid ; Structure-Activity Relationship ; Transcription Factors/*metabolism ; *Zinc Fingers
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-10-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wertman, K F -- Drubin, D G -- GM42759/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Oct 30;258(5083):759-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1439782" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*chemistry/genetics/metabolism ; Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Binding Sites ; Models, Molecular ; Molecular Structure ; Mutation ; Rabbits ; Tetrahymena/chemistry
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  • 6
    Publication Date: 1992-08-14
    Description: A pseudo--half-knot can be formed by binding an oligonucleotide asymmetrically to an RNA hairpin loop. This binding motif was used to target the human immunodeficiency virus TAR element, an important viral RNA structure that is the receptor for Tat, the major viral transactivator protein. Oligonucleotides complementary to different halves of the TAR structure bound with greater affinity than molecules designed to bind symmetrically around the hairpin. The pseudo--half-knot--forming oligonucleotides altered the TAR structure so that specific recognition and binding of a Tat-derived peptide was disrupted. This general binding motif may be used to disrupt the structure of regulatory RNA hairpins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ecker, D J -- Vickers, T A -- Bruice, T W -- Freier, S M -- Jenison, R D -- Manoharan, M -- Zounes, M -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):958-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ISIS Pharmaceuticals, Carlsbad, CA 92008.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1502560" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; DNA, Viral/metabolism ; Gene Products, tat/metabolism ; HIV/*genetics ; Kinetics ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Oligoribonucleotides/*chemistry ; RNA, Viral/*chemistry/genetics/metabolism ; tat Gene Products, Human Immunodeficiency Virus
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  • 7
    Publication Date: 1992-02-21
    Description: The gap genes of Drosophila are the first zygotic genes to respond to the maternal positional signals and establish the body pattern along the anterior-posterior axis. The gap gene knirps, required for patterning in the posterior region of the embryo, can be activated throughout the wild-type embryo and is normally repressed from the anterior and posterior sides. These results provide direct molecular evidence that the posterior morphogen system interacts in a fundamentally different manner than do hunchback and bicoid, which are responsible for anterior pattern formation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pankratz, M J -- Busch, M -- Hoch, M -- Seifert, E -- Jackle, H -- New York, N.Y. -- Science. 1992 Feb 21;255(5047):986-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck Institut fur Biophysikalische Chemie, Abteilung Molekulare Entwicklungsbiologie, Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1546296" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Cloning, Molecular ; Drosophila melanogaster/embryology/*genetics ; Gene Expression Regulation ; Genes ; Molecular Sequence Data ; Morphogenesis ; Regulatory Sequences, Nucleic Acid
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  • 8
    Publication Date: 1992-11-06
    Description: Electron transfer in nitrogenase involves a gating process initiated by MgATP (magnesium adenosine triphosphate) binding to Fe-protein. The redox site, an 4Fe:4S cluster, is structurally separated from the MgATP binding site. For MgATP hydrolysis to be coupled to electron transfer, a signal transduction mechanism is proposed that is similar to that in guanosine triphosphatase proteins. Based on the three-dimensional structure of Fe-protein, Asp125 is likely to be part of a putative transduction path. Altered Fe-protein with Glu replacing Asp has been prepared and retains the ability for the initial nucleotide-dependent conformational change. However, either MgADP or MgATP can induce the shift and Mg binding to the nucleotide is no longer essential.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolle, D -- Dean, D R -- Howard, J B -- New York, N.Y. -- Science. 1992 Nov 6;258(5084):992-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Minnesota, Minneapolis 55455.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1359643" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/*metabolism ; Aspartic Acid/*metabolism ; Azotobacter vinelandii/enzymology ; Binding Sites ; Crystallization ; Electron Transport ; Glutamates ; Glutamic Acid ; Iron-Sulfur Proteins/*metabolism ; Molecular Structure ; Mutagenesis, Site-Directed ; Nitrogenase/chemistry/genetics/*metabolism ; Protein Conformation ; Signal Transduction/*physiology
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  • 9
    Publication Date: 1992-06-26
    Description: The interaction of the T cell glycoprotein CD2 with one ligand, CD58, contributes to T cell function. We have identified CD59, a glycoprotein with complement-inhibitory function, as a second physiological ligand for CD2. Antibodies to CD59 inhibit CD2-dependent T cell activation in murine T cell hybridomas expressing human CD2. In an in vitro binding assay with purified CD58 and CD59, CD2+ cells bind not only immobilized CD58 but also CD59. With two complementary approaches, it was demonstrated that the binding sites on CD2 for CD58 and CD59 are overlapping but nonidentical. These observations suggest that direct interactions between CD2 and both CD58 and CD59 contribute to T cell activation and adhesion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hahn, W C -- Menu, E -- Bothwell, A L -- Sims, P J -- Bierer, B E -- AI28554/AI/NIAID NIH HHS/ -- HL36061/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1992 Jun 26;256(5065):1805-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pediatric Oncology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1377404" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/*metabolism ; Antigens, CD2 ; Antigens, CD58 ; Antigens, CD59 ; Antigens, Differentiation, T-Lymphocyte/*metabolism ; Binding Sites ; Dose-Response Relationship, Drug ; Humans ; Hybridomas ; Immunity, Cellular ; In Vitro Techniques ; Membrane Glycoproteins/*metabolism ; Mice ; Receptors, Antigen, T-Cell/*physiology ; Receptors, Immunologic/*metabolism ; T-Lymphocytes/immunology
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  • 10
    Publication Date: 1992-01-24
    Description: The c-Myc oncoprotein belongs to a family of proteins whose DNA binding domains contain a basic region-helix-loop-helix (bHLH) motif. Systematic mutagenesis of c-Myc revealed that dimerized bHLH motifs formed a parallel four-helix bundle with the amino termini of helices 1 and 2 directed toward the inner and outer nucleotides of the DNA binding site, respectively. Both the basic region and the carboxyl-terminal end of the loop contributed to DNA binding specificity. The DNA binding domain of c-Myc may therefore be structurally similar to that of restriction endonuclease Eco RI.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Halazonetis, T D -- Kandil, A N -- New York, N.Y. -- Science. 1992 Jan 24;255(5043):464-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Research, Merck Sharp and Dohme Research Laboratories, West Point, PA 19486.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1734524" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; DNA-Binding Proteins/*chemistry ; Deoxyribonuclease EcoRI/*chemistry ; Humans ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Protein Conformation ; Proto-Oncogene Proteins c-myc/*chemistry ; Sequence Alignment ; Transcription Factors/chemistry
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-01-10
    Description: Many specific DNA-binding proteins bind to sites with dyad symmetry, and the bound form of the protein is a dimer. For some proteins, dimers form in solution and bind to DNA. LexA repressor of Escherichia coli has been used to test an alternative binding model in which two monomers bind sequentially. This model predicts that a repressor monomer should bind with high specificity to an isolated operator half-site. Monomer binding to a half-site was observed. A second monomer bound to an intact operator far more tightly than the first monomer; this cooperativity arose from protein-protein contacts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, B -- Little, J W -- GM24178/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jan 10;255(5041):203-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Arizona, Tucson 85721.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1553548" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*metabolism ; Base Sequence ; Binding Sites ; DNA, Bacterial/*metabolism ; DNA-Binding Proteins/*metabolism ; Deoxyribonucleases ; Escherichia coli/*metabolism ; Kinetics ; Macromolecular Substances ; Models, Structural ; Molecular Sequence Data ; Oligodeoxyribonucleotides/metabolism ; Operon ; Rec A Recombinases/genetics ; Repressor Proteins/metabolism ; *Serine Endopeptidases
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  • 12
    Publication Date: 1992-09-04
    Description: The transcriptional antiterminator protein BglG inhibits transcription termination of the bgl operon in Escherichia coli when it is in the nonphosphorylated state. The BglG protein is now shown to exist in two configurations, an active, dimeric nonphosphorylated form and an inactive, monomeric phosphorylated form. The migration of BglG on native polyacrylamide gels was consistent with it existing as a dimer when nonphosphorylated and as a monomer when phosphorylated. Only the nonphosphorylated dimer was found to bind to the target RNA. When the dimerization domain of the lambda repressor was replaced with BglG, the resulting chimera behaved like an intact lambda repressor in its ability to repress lambda gene expression, which suggests that BglG dimerizes in vivo. Repression by the lambda-BglG hybrid was significantly reduced by BglF, the BglG kinase, an effect that was relieved by conditions that stimulate dephosphorylation of BglG by BglF. These results suggest that the phosphorylation and the dephosphorylation of BglG regulate its activity by controlling its dimeric state.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amster-Choder, O -- Wright, A -- New York, N.Y. -- Science. 1992 Sep 4;257(5075):1395-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Microbiology, Tufts University Health Sciences Campus, Boston, MA 02111.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1382312" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/metabolism ; Bacteriophage lambda/genetics ; Binding Sites ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli/metabolism ; Macromolecular Substances ; Molecular Weight ; Operon ; Phosphorylation ; RNA/metabolism ; RNA-Binding Proteins/*chemistry/metabolism ; Repressor Proteins/metabolism ; Structure-Activity Relationship ; Transcription, Genetic
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  • 13
    Publication Date: 1992-08-07
    Description: A Src homology 3 (SH3) region is a sequence of approximately 50 amino acids found in many nonreceptor tyrosine kinases and other proteins. Deletion of the SH3 region from the protein encoded by the c-abl proto-oncogene activates the protein's transforming capacity, thereby suggesting the participation of the SH3 region in the negative regulation of transformation. A complementary DNA was isolated that encoded a protein, 3BP-1, to which the SH3 region of Abl bound with high specificity and to which SH3 regions from other proteins bound differentially. The sequence of the 3BP-1 protein is similar to that of a COOH-terminal segment of Bcr and to guanosine triphosphatase-activating protein (GAP)-rho, which suggests that it might have GAP activity for Ras-related proteins. The 3BP-1 protein may therefore be a mediator of SH3 function in transformation inhibition and may link tyrosine kinases to Ras-related proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cicchetti, P -- Mayer, B J -- Thiel, G -- Baltimore, D -- A107233/PHS HHS/ -- CA 08875/CA/NCI NIH HHS/ -- CA51462/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 7;257(5071):803-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1379745" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Amino Acid Sequence ; Animals ; Binding Sites ; Chimera ; Cloning, Molecular ; GTPase-Activating Proteins ; Gene Library ; *Genes, abl ; *Genes, src ; Glutathione Transferase/genetics/metabolism ; Mice ; Molecular Sequence Data ; Oncogene Proteins/genetics/*metabolism ; Plasmids ; Polymerase Chain Reaction/methods ; Prosencephalon/physiology ; Protein-Tyrosine Kinases/*metabolism ; Proteins/*metabolism ; *Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-abl/genetics/*metabolism ; Proto-Oncogene Proteins c-bcr ; Proto-Oncogene Proteins pp60(c-src)/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Restriction Mapping ; Rho Factor/*metabolism ; Sequence Homology, Nucleic Acid ; ras GTPase-Activating Proteins
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-03-06
    Description: Trypsin (Tr) and chymotrypsin (Ch) have similar tertiary structures, yet Tr cleaves peptides at arginine and lysine residues and Ch prefers large hydrophobic residues. Although replacement of the S1 binding site of Tr with the analogous residues of Ch is sufficient to transfer Ch specificity for ester hydrolysis, specificity for amide hydrolysis is not transferred. Trypsin is converted to a Ch-like protease when the binding pocket alterations are further modified by exchange of the Ch surface loops 185 through 188 and 221 through 225 for the analogous Tr loops. These loops are not structural components of either the S1 binding site or the extended substrate binding sites. This mutant enzyme is equivalent to Ch in its catalytic rate, but its substrate binding is impaired. Like Ch, this mutant utilizes extended substrate binding to accelerate catalysis, and substrate discrimination occurs during the acylation step rather than in substrate binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hedstrom, L -- Szilagyi, L -- Rutter, W J -- DK21344/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1992 Mar 6;255(5049):1249-53.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Hormone Research Institute, University of California, San Francisco 94143-0534.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1546324" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Amino Acid Sequence ; Base Sequence ; Binding Sites ; Chymotrypsin/*chemistry/metabolism ; Hydrolysis ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Mutagenesis, Site-Directed ; Protein Conformation ; Substrate Specificity ; Trypsin/*chemistry/genetics/metabolism
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  • 15
    Publication Date: 1992-09-04
    Description: Yeast RNA polymerase II initiation factor b copurifies with three polypeptides of 85, 73, and 50 kilodaltons and with a protein kinase that phosphorylates the carboxyl-terminal repeat domain (CTD) of the largest polymerase subunit. The gene that encodes the 73-kilodalton polypeptide, designated TFB1, was cloned and found to be essential for cell growth. The deduced protein sequence exhibits no similarity to those of protein kinases. However, the sequence is similar to that of the 62-kilodalton subunit of the HeLa transcription factor BFT2, suggesting that this factor is the human counterpart of yeast factor b. Immunoprecipitation experiments using antibodies to the TFB1 gene product demonstrate that the transcriptional and CTD kinase activities of factor b are closely associated with an oligomer of the three polypeptides. Photoaffinity labeling with 3'-O-(4-benzoyl)benzoyl-ATP (adenosine triphosphate) identified an ATP-binding site in the 85-kilodalton polypeptide, suggesting that the 85-kilodalton subunit contains the catalytic domain of the kinase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gileadi, O -- Feaver, W J -- Kornberg, R D -- GM-36659/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Sep 4;257(5075):1389-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Sherman Fairchild Center, Stanford University Medical School, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1445600" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Affinity Labels ; Amino Acid Sequence ; Base Sequence ; Binding Sites ; *Cloning, Molecular ; Immunosorbent Techniques ; Molecular Sequence Data ; Phosphorylation ; Protein Kinases/chemistry/*genetics/metabolism ; RNA Polymerase II/metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; *Saccharomyces cerevisiae Proteins ; Sequence Homology, Nucleic Acid ; Transcription Factors/chemistry/*genetics ; *Transcription Factors, General ; *Transcription Factors, TFII ; *Transcriptional Elongation Factors
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  • 16
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-24
    Description: A cleavage reagent directed to the active site of the Tetrahymena catalytic RNA was synthesized by derivatization of the guanosine substrate with a metal chelator. When complexed with iron(II), this reagent cleaved the RNA in five regions. Cleavage at adenosine 207, which is far from the guanosine-binding site in the primary and secondary structure, provides a constraint for the higher order folding of the RNA. This cleavage site constitutes physical evidence for a key feature of the Michel-Westhof model. Targeting a reactive entity to a specific site should be generally useful for determining proximity within folded RNA molecules or ribonucleoprotein complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, J F -- Cech, T R -- New York, N.Y. -- Science. 1992 Apr 24;256(5056):526-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309-0215.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1315076" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Edetic Acid/metabolism ; Free Radicals ; Guanosine/*metabolism ; Guanosine Monophosphate/metabolism ; Iron/metabolism ; Iron Chelating Agents/metabolism ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Nucleic Acid Conformation ; Pentetic Acid/metabolism ; RNA, Catalytic/*chemistry/metabolism ; Tetrahymena/*chemistry
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  • 17
    Publication Date: 1992-05-15
    Description: A facile method for isolating genes that encode interacting proteins has been developed with a polypeptide probe that contains an amino-terminal extension with recognition sites for a monoclonal antibody, a specific endopeptidase, and a site-specific protein kinase. This probe, containing the basic region-leucine zipper dimerization motif of c-Fos, was used to screen a complementary DNA library. A complementary DNA that encoded a member of the basic-helix-loop-helix-zipper (bHLH-Zip) family of proteins was isolated. The complementary DNA-encoded polypeptide FIP (Fos interacting protein) bound to oligonucleotide probes that contained DNA binding motifs for other HLH proteins. When cotransfected with c-Fos, FIP stimulated transcription of an AP-1-responsive promoter.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blanar, M A -- Rutter, W J -- DK-21344/DK/NIDDK NIH HHS/ -- DK-41822/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1992 May 15;256(5059):1014-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Hormone Research Institute, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1589769" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; *Cloning, Molecular ; DNA/isolation & purification ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; *Genes, fos/genetics ; HeLa Cells ; Humans ; Leucine Zippers/*genetics ; Macromolecular Substances ; Molecular Sequence Data ; Oligonucleotide Probes/chemistry/metabolism ; Protein Conformation ; Proto-Oncogene Proteins c-fos/chemistry/metabolism ; Proto-Oncogene Proteins c-jun/chemistry/metabolism ; Sequence Homology, Nucleic Acid ; Transfection
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  • 18
    Publication Date: 1992-12-21
    Description: Interferon-gamma (IFN-gamma) induces the transcription of the gene encoding a guanylate binding protein by activating a latent cytoplasmic factor, GAF (gamma-activated factor). GAF is translocated to the nucleus and binds a DNA element, the gamma-activated site. Through cross-linking and the use of specific antibodies GAF was found to be a 91-kilodalton DNA binding protein that was previously identified as one of four proteins in interferon-stimulated gene factor-3 (ISGF-3), a transcription complex activated by IFN-alpha. The IFN-gamma-dependent activation of the 91-kilodalton DNA binding protein required cytoplasmic phosphorylation of the protein on tyrosine. The 113-kilodalton ISGF-3 protein that is phosphorylated in response to IFN-alpha was not phosphorylated nor translocated to the nucleus in response to IFN-gamma. Thus the two different ligands result in tyrosine phosphorylation of different combinations of latent cytoplasmic transcription factors that then act at different DNA binding sites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shuai, K -- Schindler, C -- Prezioso, V R -- Darnell, J E Jr -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1808-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1281555" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Cell Line ; Cell Nucleus/metabolism ; DNA-Binding Proteins/isolation & purification/*metabolism ; Electrophoresis, Gel, Two-Dimensional ; Electrophoresis, Polyacrylamide Gel ; GTP-Binding Proteins/*genetics ; Gene Expression Regulation/drug effects ; Interferon-alpha/pharmacology ; Interferon-gamma/*pharmacology ; Models, Biological ; Molecular Sequence Data ; Molecular Weight ; Oligodeoxyribonucleotides ; Phosphorylation ; Phosphotyrosine ; Promoter Regions, Genetic ; STAT1 Transcription Factor ; Signal Transduction/drug effects ; *Trans-Activators ; *Transcription, Genetic/drug effects ; Tyrosine/analogs & derivatives/analysis
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  • 19
    Publication Date: 1992-08-21
    Description: Cells with distinct developmental histories can respond differentially to identical signals, suggesting that signals are interpreted in a fashion that reflects a cell's identity. How this might occur is suggested by the observation that proteins of the homeodomain family, including a newly identified human protein, enhance the DNA-binding activity of serum response factor, a protein required for the induction of genes by growth and differentiation factors. Interaction with proteins of the serum response factor family may allow homeodomain proteins to specify the transcriptional response to inductive signals. Moreover, because the ability to enhance the binding of serum response factor to DNA residues within the homeodomain but is independent of homeodomain DNA-binding activity, this additional activity of the homeodomain may account for some of specificity of action of homeodomain proteins in development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grueneberg, D A -- Natesan, S -- Alexandre, C -- Gilman, M Z -- CA08968/CA/NCI NIH HHS/ -- CA45642/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 21;257(5073):1089-95.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, NY 11724.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1509260" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; DNA/genetics/*metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism/*pharmacology ; Drosophila/genetics ; *Drosophila Proteins ; Fungal Proteins/chemistry/pharmacology ; *Homeodomain Proteins ; Humans ; Minichromosome Maintenance 1 Protein ; Molecular Sequence Data ; Nuclear Proteins/*metabolism ; Saccharomyces cerevisiae/genetics ; Serum Response Factor ; Transcription Factors/chemistry/*metabolism/pharmacology ; Transfection
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  • 20
    Publication Date: 1992-01-17
    Description: Binding of human growth hormone (hGH) to its receptor is required for regulation of normal human growth and development. Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor. The hormone is a four-helix bundle with an unusual topology. The binding protein contains two distinct domains, similar in some respects to immunoglobulin domains. The relative orientation of these domains differs from that found between constant and variable domains in immunoglobulin Fab fragments. Both hGHbp domains contribute residues that participate in hGH binding. In the complex both receptors donate essentially the same residues to interact with the hormone, even though the two binding sites on hGH have no structural similarity. Generally, the hormone-receptor interfaces match those identified by previous mutational analyses. In addition to the hormone-receptor interfaces, there is also a substantial contact surface between the carboxyl-terminal domains of the receptors. The relative extents of the contact areas support a sequential mechanism for dimerization that may be crucial for signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Vos, A M -- Ultsch, M -- Kossiakoff, A A -- New York, N.Y. -- Science. 1992 Jan 17;255(5042):306-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1549776" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography ; Growth Hormone/*chemistry/metabolism ; Humans ; Hydrogen Bonding ; Models, Molecular ; Molecular Structure ; Mutation ; Receptors, Somatotropin/*chemistry/metabolism ; Signal Transduction
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  • 21
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-06-05
    Description: Regulation of interleukin-2 (IL-2) gene expression by the p50 and p65 subunits of the DNA binding protein NF-kappa B was studied in nontransformed CD4+ T lymphocyte clones. A homodimeric complex of the NF-kappa B p50 subunit was found in resting T cells. The amount of p50-p50 complex decreased after full antigenic stimulation, whereas the amount of the NF-kappa B p50-p65 heterodimer was increased. Increased expression of the IL-2 gene and activity of the IL-2 kappa B DNA binding site correlated with a decrease in the p50-p50 complex. Overexpression of p50 repressed IL-2 promoter expression. The switch from p50-p50 to p50-p65 complexes depended on a protein that caused sequestration of the p50-p50 complex in the nucleus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, S M -- Tran, A C -- Grilli, M -- Lenardo, M J -- New York, N.Y. -- Science. 1992 Jun 5;256(5062):1452-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunology, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1604322" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/*immunology ; Base Sequence ; Binding Sites ; Cell Line ; Cell Nucleus/physiology ; Chloramphenicol O-Acetyltransferase/genetics/metabolism ; Clone Cells ; Columbidae ; DNA/genetics ; *Gene Expression Regulation ; Interleukin-2/*genetics ; Macromolecular Substances ; Mice ; Molecular Sequence Data ; NF-kappa B/*metabolism ; Oligonucleotide Probes ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Recombinant Fusion Proteins/metabolism ; T-Lymphocyte Subsets/*immunology ; Transfection ; Tumor Necrosis Factor-alpha/pharmacology
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  • 22
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-17
    Description: The Escherichia coli Rep helicase unwinds duplex DNA during replication. The functional helicase appears to be a dimer that forms only on binding DNA. Both protomers of the dimer can bind either single-stranded or duplex DNA. Because binding and hydrolysis of adenosine triphosphate (ATP) are essential for helicase function, the energetics of DNA binding and DNA-induced Rep dimerization were studied quantitatively in the presence of the nucleotide cofactors adenosine diphosphate (ADP) and the nonhydrolyzable ATP analog AMPP(NH)P. Large allosteric effects of nucleotide cofactors on DNA binding to Rep were observed. Binding of ADP favored Rep dimers in which both protomers bound single-stranded DNA, whereas binding of AMPP(NH)P favored simultaneous binding of both single-stranded and duplex DNA to the Rep dimer. A rolling model for the active unwinding of duplex DNA by the dimeric Rep helicase is proposed that explains vectorial unwinding and predicts that helicase translocation along DNA is coupled to ATP binding, whereas ATP hydrolysis drives unwinding of multiple DNA base pairs for each catalytic event.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wong, I -- Lohman, T M -- GM30498/GM/NIGMS NIH HHS/ -- GM45948/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 17;256(5055):350-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1533057" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine Nucleotides/*pharmacology ; Adenosine Diphosphate/metabolism/pharmacology ; Adenosine Triphosphatases/*metabolism ; Adenosine Triphosphate/metabolism ; Adenylyl Imidodiphosphate/pharmacology ; Base Sequence ; Binding Sites ; Binding, Competitive ; DNA/chemistry/*metabolism ; *DNA Helicases ; DNA, Single-Stranded/metabolism ; DNA, Viral/metabolism ; Escherichia coli/*enzymology ; Escherichia coli Proteins ; Macromolecular Substances ; Magnesium/pharmacology ; Molecular Sequence Data ; Nucleic Acid Conformation
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  • 23
    Publication Date: 1992-07-03
    Description: Aldose reductase, which catalyzes the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of a wide variety of aromatic and aliphatic carbonyl compounds, is implicated in the development of diabetic and galactosemic complications involving the lens, retina, nerves, and kidney. A 1.65 angstrom refined structure of a recombinant human placenta aldose reductase reveals that the enzyme contains a parallel beta 8/alpha 8-barrel motif and establishes a new motif for NADP-binding oxidoreductases. The substrate-binding site is located in a large, deep elliptical pocket at the COOH-terminal end of the beta barrel with a bound NADPH in an extended conformation. The highly hydrophobic nature of the active site pocket greatly favors aromatic and apolar substrates over highly polar monosaccharides. The structure should allow for the rational design of specific inhibitors that might provide molecular understanding of the catalytic mechanism, as well as possible therapeutic agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, D K -- Bohren, K M -- Gabbay, K H -- Quiocho, F A -- DK-39,044/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1992 Jul 3;257(5066):81-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1621098" target="_blank"〉PubMed〈/a〉
    Keywords: Aldehyde Reductase/*chemistry/metabolism ; Amino Acid Sequence ; Binding Sites ; *Diabetes Complications ; Diabetes Mellitus/*enzymology ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; X-Ray Diffraction/methods
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  • 24
    Publication Date: 1992-04-03
    Description: Steroid-thyroid hormone receptors typically bind as dimers to DNA sequences that contain repeated elements termed half-sites. NGFI-B, an early response protein and orphan member of this receptor superfamily, binds to a DNA sequence that contains only one half-site (5'-AAAGGTCA-3'). A domain separate from the NGFI-B zinc fingers, termed the A box, was identified and is required for recognition of the two adenine-thymidine (A-T) base pairs at the 5' end of the NGFI-B DNA binding element. In addition, a domain downstream of the zinc fingers of the orphan receptor H-2 region II binding protein, termed the T box, determined binding to tandem repeats of the estrogen receptor half-site (5'-AGGTCA-3').〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, T E -- Paulsen, R E -- Padgett, K A -- Milbrandt, J -- NS01018/NS/NINDS NIH HHS/ -- P01 CA49712/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 3;256(5053):107-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1314418" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; CHO Cells ; Cell Nucleus/*physiology ; Cricetinae ; DNA/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Kinetics ; Mice ; Molecular Sequence Data ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Oligodeoxyribonucleotides/metabolism ; Polymerase Chain Reaction ; Receptors, Cell Surface/*metabolism ; Receptors, Cytoplasmic and Nuclear ; Receptors, Steroid ; Recombinant Fusion Proteins/metabolism ; Sequence Homology, Nucleic Acid ; Substrate Specificity ; Transcription Factors/genetics/*metabolism ; Transfection ; Zinc Fingers/genetics
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  • 25
    Publication Date: 1992-12-11
    Description: The crystal structure of a 1:1 complex between yeast cytochrome c peroxidase and yeast iso-1-cytochrome c was determined at 2.3 A resolution. This structure reveals a possible electron transfer pathway unlike any previously proposed for this extensively studied redox pair. The shortest straight line between the two hemes closely follows the peroxidase backbone chain of residues Ala194, Ala193, Gly192, and finally Trp191, the indole ring of which is perpendicular to, and in van der Waals contact with, the peroxidase heme. The crystal structure at 2.8 A of a complex between yeast cytochrome c peroxidase and horse heart cytochrome c was also determined. Although crystals of the two complexes (one with cytochrome c from yeast and the other with cytochrome c from horse) grew under very different conditions and belong to different space groups, the two complex structures are closely similar, suggesting that cytochrome c interacts with its redox partners in a highly specific manner.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pelletier, H -- Kraut, J -- DK07233/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1748-55.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, San Diego, La Jolla 92093-0317.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1334573" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cytochrome c Group/*chemistry/metabolism ; Cytochrome-c Peroxidase/*chemistry/metabolism ; *Electron Transport ; Heme/metabolism ; Horses ; Models, Molecular ; Molecular Sequence Data ; *Protein Conformation ; Saccharomyces cerevisiae/metabolism ; X-Ray Diffraction/methods
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  • 26
    Publication Date: 1992-09-04
    Description: The N-methyl-D-aspartate (NMDA) receptor forms a cation-selective channel with a high calcium permeability and sensitivity to channel block by extracellular magnesium. These properties, which are believed to be important for the induction of long-term changes in synaptic strength, are imparted by asparagine residues in a putative channel-forming segment of the protein, transmembrane 2 (TM2). In the NR1 subunit, replacement of this asparagine by a glutamine residue decreases calcium permeability of the channel and slightly reduces magnesium block. The same substitution in NR2 subunits strongly reduces magnesium block and increases the magnesium permeability but barely affects calcium permeability. These asparagines are in a position homologous to the site in the TM2 region (Q/R site) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that is occupied by either glutamine (Q) or arginine (R) and that controls divalent cation permeability of the AMPA receptor channel. Hence AMPA and NMDA receptor channels contain common structural motifs in their TM2 segments that are responsible for some of their ion selectivity and conductance properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burnashev, N -- Schoepfer, R -- Monyer, H -- Ruppersberg, J P -- Gunther, W -- Seeburg, P H -- Sakmann, B -- New York, N.Y. -- Science. 1992 Sep 4;257(5075):1415-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abteilung Zellphysiologie, Max-Planck-Institut fur Medizinische Forschung, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1382314" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Asparagine/*chemistry ; Binding Sites ; Calcium/*metabolism/pharmacology ; Cell Line ; Electric Conductivity ; Glutamates/pharmacology ; Glutamic Acid ; Ion Channels/chemistry/*physiology ; Magnesium/metabolism/*pharmacology ; Mice ; Molecular Sequence Data ; Mutagenesis ; Oocytes/metabolism ; Permeability ; Rats ; Receptors, N-Methyl-D-Aspartate/chemistry/genetics/*physiology ; Structure-Activity Relationship ; Transfection ; Xenopus
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  • 27
    Publication Date: 1992-06-05
    Description: Several classes of ribozymes (catalytic RNA's) catalyze reactions at phosphorus centers, but apparently no reaction at a carbon center has been demonstrated. The active site of the Tetrahymena ribozyme was engineered to bind an oligonucleotide derived from the 3' end of N-formyl-methionyl-tRNA(fMet). This ribozyme catalyzes the hydrolysis of the aminoacyl ester bond to a modest extent, 5 to 15 times greater than the uncatalyzed rate. Catalysis involves binding of the oligonucleotide to the internal guide sequence of the ribozyme and requires Mg2+ and sequence elements of the catalytic core. The ability of RNA to catalyze reactions with aminoacyl esters expands the catalytic versatility of RNA and suggests that the first aminoacyl tRNA synthetase could have been an RNA molecule.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Piccirilli, J A -- McConnell, T S -- Zaug, A J -- Noller, H F -- Cech, T R -- New York, N.Y. -- Science. 1992 Jun 5;256(5062):1420-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1604316" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Carboxylic Ester Hydrolases/*metabolism ; Kinetics ; Models, Structural ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligoribonucleotides ; RNA, Catalytic/genetics/*metabolism ; RNA, Transfer, Amino Acyl/metabolism ; *RNA, Transfer, Met ; Substrate Specificity ; Tetrahymena/*enzymology
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  • 28
    Publication Date: 1992-01-03
    Description: The p107 protein and the retinoblastoma protein (RB) both bind specifically to two viral oncoproteins, the SV40 T antigen (T) and adenoviral protein E1A (E1A). Like RB, p107 contains a segment (the pocket) that, alone, can bind specifically to T, E1A, and multiple cellular proteins. Cyclin A bound to the p107 pocket, but not the RB pocket. Although both pockets contain two, related collinear subsegments (A and B), the unique sequence in the p107 pocket that occupies the space between A and B is required for the interaction with cyclin A.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ewen, M E -- Faha, B -- Harlow, E -- Livingston, D M -- New York, N.Y. -- Science. 1992 Jan 3;255(5040):85-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1532457" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus Early Proteins ; Amino Acid Sequence ; Antigens, Polyomavirus Transforming/*metabolism ; Base Sequence ; Binding Sites ; Cell Line ; Cloning, Molecular ; Cyclins/*metabolism ; Escherichia coli/genetics ; Eye Neoplasms ; Glutathione Transferase/genetics/metabolism ; Humans ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; *Nuclear Proteins ; Oligodeoxyribonucleotides ; Oncogene Proteins, Viral/genetics/*metabolism ; Protein Conformation ; Proteins/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Retinoblastoma ; Retinoblastoma Protein/genetics/*metabolism ; Retinoblastoma-Like Protein p107 ; Structure-Activity Relationship
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  • 29
    Publication Date: 1992-08-14
    Description: Class I major histocompatibility complex (MHC) molecules interact with self and foreign peptides of diverse amino acid sequences yet exhibit distinct allele-specific selectivity for peptide binding. The structures of the peptide-binding specificity pockets (subsites) in the groove of murine H-2Kb as well as human histocompatibility antigen class I molecules have been analyzed. Deep but highly conserved pockets at each end of the groove bind the amino and carboxyl termini of peptide through extensive hydrogen bonding and, hence, dictate the orientation of peptide binding. A deep polymorphic pocket in the middle of the groove provides the chemical and structural complementarity for one of the peptide's anchor residues, thereby playing a major role in allele-specific peptide binding. Although one or two shallow pockets in the groove may also interact with specific peptide side chains, their role in the selection of peptide is minor. Thus, usage of a limited number of both deep and shallow pockets in multiple combinations appears to allow the binding of a broad range of peptides. This binding occurs with high affinity, primarily because of extensive interactions with the peptide backbone and the conserved hydrogen bonding network at both termini of the peptide. Interactions between the anchor residue (or residues) and the corresponding allele-specific pocket provide sufficient extra binding affinity not only to enhance specificity but also to endure the presentation of the peptide at the cell surface for recognition by T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsumura, M -- Fremont, D H -- Peterson, P A -- Wilson, I A -- CA-09523/CA/NCI NIH HHS/ -- CA-97489/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):927-34.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1323878" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens/chemistry/*metabolism ; Binding Sites ; H-2 Antigens/chemistry/*metabolism ; HLA-A2 Antigen/chemistry ; Histocompatibility Antigens Class I/chemistry/*metabolism ; Hydrogen Bonding ; Mice ; Models, Molecular ; Molecular Sequence Data ; Ovalbumin/chemistry/metabolism ; Peptide Fragments/chemistry/metabolism ; Peptides/chemistry/*metabolism ; Protein Conformation ; Solvents ; Vesicular stomatitis Indiana virus/metabolism ; Viral Proteins/chemistry/*metabolism
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-12-11
    Description: When template DNA is saturated with a single-stranded DNA binding protein (SSB), strings of three or four contiguous hexanucleotides (hexamers) can cooperate through base-stacking interactions to prime DNA synthesis specifically from the 3' end of the string. Under the same conditions, priming by individual hexamers is suppressed. Strings of three of four hexamers representing more than 200 of the 4096 possible hexamers primed easily readable sequence ladders at more than 75 different sites in single-stranded or denatured double-stranded templates 6.4 kilobases to 40 kilobase pairs long, with a success rate of 60 to 90 percent. A synthesis of 1 micromole of hexamer supplies enough material for thousands of primings, so multiple libraries of all 4096 hexamers could be distributed at a reasonable cost. Such libraries would allow rapid and economical sequencing. Automating this strategy could increase the speed and efficiency of large-scale DNA sequencing by at least an order of magnitude.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kieleczawa, J -- Dunn, J J -- Studier, F W -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1787-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department, Brookhaven National Laboratory, Upton, NY 11973.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1465615" target="_blank"〉PubMed〈/a〉
    Keywords: *Base Sequence ; Binding Sites ; DNA/*genetics/metabolism ; DNA, Viral/genetics ; DNA-Binding Proteins/metabolism ; Escherichia coli/metabolism ; *Genetic Techniques ; Molecular Sequence Data ; Nucleic Acid Denaturation ; Oligodeoxyribonucleotides ; Sulfur Radioisotopes ; Templates, Genetic
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  • 31
    Publication Date: 1992-12-04
    Description: The Src homology 3 (SH3) region is a protein domain of 55 to 75 amino acids found in many cytoplasmic proteins, including those that participate in signal transduction pathways. The solution structure of the SH3 domain of the tyrosine kinase Src was determined by multidimensional nuclear magnetic resonance methods. The molecule is composed of two short three-stranded anti-parallel beta sheets packed together at approximately right angles. Studies of the SH3 domain bound to proline-rich peptide ligands revealed a hydrophobic binding site on the surface of the protein that is lined with the side chains of conserved aromatic amino acids.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, H -- Rosen, M K -- Shin, T B -- Seidel-Dugan, C -- Brugge, J S -- Schreiber, S L -- 1-S10-RR04870/RR/NCRR NIH HHS/ -- CA27951/CA/NCI NIH HHS/ -- GM44993/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 4;258(5088):1665-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1280858" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cloning, Molecular ; Escherichia coli/genetics ; Glutathione Transferase/chemistry/genetics/isolation & purification ; Ligands ; Magnetic Resonance Spectroscopy ; Molecular Sequence Data ; Neurons/physiology ; Protein Conformation ; *Protein Structure, Secondary ; Protein-Tyrosine Kinases/*genetics ; Proto-Oncogene Proteins pp60(c-src)/*chemistry ; Recombinant Fusion Proteins/chemistry/isolation & purification ; Solutions ; X-Ray Diffraction
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-15
    Description: The heterotrimeric guanine nucleotide binding proteins (G proteins) are activated by sensory or hormone receptors. In turn, the G proteins activate effector proteins such as adenylyl cyclase, cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP PDE), phospholipase C, and potassium and calcium ion channels by mechanisms that are poorly understood. A site on the alpha subunit of the G protein transducin (alpha t) has been identified that interacts with and activates cGMP phosphodiesterase, the effector enzyme in rod photoreceptors. A 22-amino acid peptide, corresponding to residues 293 to 314 from the COOH-terminal region of alpha t, fully mimicked alpha t and potently activated PDE. This region is adjacent to the receptor activation domain; thus, the alpha subunit of this G protein has a site for interaction with both its effector and receptor that maps near the COOH-terminus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rarick, H M -- Artemyev, N O -- Hamm, H E -- EY 06062/EY/NEI NIH HHS/ -- T32 HL 07692-02/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1992 May 15;256(5059):1031-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60680.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1317058" target="_blank"〉PubMed〈/a〉
    Keywords: 3',5'-Cyclic-GMP Phosphodiesterases/*metabolism ; Amino Acid Sequence ; Animals ; Binding Sites ; Cattle ; Chromatography, High Pressure Liquid ; Enzyme Activation/drug effects ; GTP-Binding Proteins/*chemistry/*physiology ; Guanosine 5'-O-(3-Thiotriphosphate)/metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; Macromolecular Substances ; Molecular Sequence Data ; Peptide Fragments/chemistry/*pharmacology ; Protein Conformation
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  • 33
    Publication Date: 1992-06-26
    Description: A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer. The polymerase (pol) domain of the 66-kilodalton subunit has a large cleft analogous to that of the Klenow fragment of Escherichia coli DNA polymerase I. However, the 51-kilodalton subunit of identical sequence has no such cleft because the four subdomains of the pol domain occupy completely different relative positions. Two of the four pol subdomains appear to be structurally related to subdomains of the Klenow fragment, including one containing the catalytic site. The subdomain that appears likely to bind the template strand at the pol active site has a different structure in the two polymerases. Duplex A-form RNA-DNA hybrid can be model-built into the cleft that runs between the ribonuclease H and pol active sites. Nevirapine is almost completely buried in a pocket near but not overlapping with the pol active site. Residues whose mutation results in drug resistance have been approximately located.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kohlstaedt, L A -- Wang, J -- Friedman, J M -- Rice, P A -- Steitz, T A -- GM 39546/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jun 26;256(5065):1783-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1377403" target="_blank"〉PubMed〈/a〉
    Keywords: Azepines/pharmacology ; Binding Sites ; Crystallography ; DNA Polymerase I/chemistry ; Escherichia coli/genetics ; HIV-1/*enzymology ; Models, Molecular ; Molecular Structure ; Nevirapine ; Protein Conformation ; Pyridines/pharmacology ; RNA-Directed DNA Polymerase/*chemistry
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, S H -- New York, N.Y. -- Science. 1992 Mar 6;255(5049):1217-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1546321" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallization ; DNA/*chemistry/metabolism ; Models, Molecular ; Molecular Structure ; *Nucleic Acid Conformation
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  • 35
    Publication Date: 1992-09-18
    Description: The double-stranded RNA-dependent protein kinase (dsRNA-PK) is thought to be a key mediator of the antiviral and antiproliferative effects of interferons (IFNs). Studies examining the physiological function of the kinase suggest that it participates in cell growth and differentiation by regulating protein synthesis. Autophosphorylation and consequent activation of dsRNA-PK in vitro and in vivo result in phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2) and inhibition of protein synthesis. Expression of a functionally defective mutant of human dsRNA-PK in NIH 3T3 cells resulted in malignant transformation, suggesting that dsRNA-PK may function as a suppressor of cell proliferation and tumorigenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koromilas, A E -- Roy, S -- Barber, G N -- Katze, M G -- Sonenberg, N -- AI22646/AI/NIAID NIH HHS/ -- RR00166/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1992 Sep 18;257(5077):1685-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1382315" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Cell Division ; Cell Line ; *Cell Transformation, Neoplastic ; Cloning, Molecular ; DNA/genetics ; Enzyme Induction ; Gene Expression ; Humans ; Immunoblotting ; Interferons/*pharmacology ; Mice ; Molecular Sequence Data ; *Mutation ; Phosphorylation ; Protein Kinases/chemistry/*genetics/physiology ; Transfection ; eIF-2 Kinase
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-17
    Description: The proto-oncogene c-abl encodes a protein tyrosine kinase that is localized in the cytoplasm and the nucleus. The large carboxyl-terminal segment of c-Abl was found to contain a DNA-binding domain that was necessary for the association of c-Abl with chromatin. The DNA-binding activity of c-Abl was lost during mitosis when the carboxyl-terminal segment became phosphorylated. In vitro phosphorylation of the DNA-binding domain by cdc2 kinase abolished DNA binding. Homozygous mutant mice expressing a c-Abl tyrosine kinase without the DNA-binding domain have been reported to die of multiple defects at birth. Thus, binding of the c-Abl tyrosine kinase to DNA may be essential to its biological function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kipreos, E T -- Wang, J Y -- CA 43054/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 17;256(5055):382-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California San Diego, La Jolla 92093-0116.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1566087" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cell Cycle/*physiology ; Chromatography, Affinity ; DNA/*metabolism ; *Genes, abl ; Mice ; Molecular Sequence Data ; Mutagenesis ; Phosphorylation ; Phosphoserine/metabolism ; Phosphothreonine/metabolism ; Protein-Tyrosine Kinases/chemistry/genetics/*metabolism ; Proto-Oncogene Proteins c-abl/chemistry/genetics/*metabolism ; Structure-Activity Relationship
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  • 37
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-17
    Description: Alterations in intracellular calcium levels activate several signal transduction pathways resulting in distinct patterns of gene expression. Here, a pathway for calcium-mediated signals is demonstrated that involves C/EBP beta, a member of the bZip family of transcription factors. In pituitary cells C/EBP beta was phosphorylated in response to increased intracellular calcium concentrations as a consequence of the activation of a calcium-calmodulin-dependent protein kinase. Phosphorylation of serine at position 276 within the leucine zipper of C/EBP beta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBP beta.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wegner, M -- Cao, Z -- Rosenfeld, M G -- New York, N.Y. -- Science. 1992 Apr 17;256(5055):370-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California, San Diego, La Jolla 92093-0648.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1314426" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; CCAAT-Enhancer-Binding Proteins ; Calcimycin/pharmacology ; Calcium/*pharmacology ; Calcium-Calmodulin-Dependent Protein Kinases ; Cell Line ; DNA/chemistry/genetics/metabolism ; DNA-Binding Proteins/chemistry/*metabolism ; Enzyme Activation/drug effects ; *Leucine Zippers ; Molecular Sequence Data ; Nuclear Proteins/chemistry/*metabolism ; Phosphorylation ; Phosphoserine/metabolism ; Pituitary Gland/metabolism ; Protein Kinases/metabolism ; Signal Transduction/drug effects ; Transcription Factors/chemistry/*metabolism ; Transcription, Genetic/drug effects ; Transfection
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  • 38
    Publication Date: 1992-08-21
    Description: Anergy is a mechanism of T lymphocyte tolerance induced by antigen receptor stimulation in the absence of co-stimulation. Anergic T cells were shown to have a defect in antigen-induced transcription of the interleukin-2 gene. Analysis of the promoter indicated that the transcription factor AP-1 and its corresponding cis element were specifically down-regulated. Exposure of anergic T cells to interleukin-2 restored both antigen responsiveness and activity of the AP-1 element.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, S M -- Beverly, B -- Tran, A C -- Brorson, K -- Schwartz, R H -- Lenardo, M J -- New York, N.Y. -- Science. 1992 Aug 21;257(5073):1134-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1509265" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; Antigens/*immunology ; Base Sequence ; Binding Sites ; Blotting, Northern ; Cell Line ; Concanavalin A/pharmacology ; *Gene Expression Regulation ; *Immune Tolerance ; Interleukin-2/*genetics/pharmacology ; Mice ; Molecular Sequence Data ; Mutation ; Promoter Regions, Genetic/genetics ; Proto-Oncogene Proteins c-jun/*physiology ; RNA, Messenger/metabolism ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/*immunology ; Transcription, Genetic ; Transfection
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  • 39
    Publication Date: 1992-10-02
    Description: The smooth muscle myosin light chain kinase (smMLCK) catalytic core was modeled by using the crystallographic coordinates of the cyclic AMP-dependent protein kinase catalytic subunit (cAPK) and a bound pseudosubstrate inhibitor peptide, PKI(5-24). Despite only 30% identity in amino acid sequence, the MLCK sequence can be readily accommodated in this structure. With the exception of the short B-helix, all major elements of secondary structure in the core are very likely conserved. The active site of the modeled MLCK complements the known requirements for peptide substrate recognition. MLCK contains a pseudosubstrate sequence that overlaps the calmodulin binding domain and has been proposed to act as an intrasteric inhibitor and occupy the substrate binding site in the absence of Ca(2+)-calmodulin. The pseudosubstrate sequence can be modeled easily into the entire backbone of PKI(5-24). The results demonstrate that the intrasteric model for regulation of MLCK by intramolecular competitive inhibition is structurally plausible.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knighton, D R -- Pearson, R B -- Sowadski, J M -- Means, A R -- Ten Eyck, L F -- Taylor, S S -- Kemp, B E -- T32CA09523/CA/NCI NIH HHS/ -- T32DK07233/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1992 Oct 2;258(5079):130-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California San Diego, La Jolla 92093-0654.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1439761" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Chromosome Mapping ; Crystallography ; *Gene Expression Regulation, Enzymologic ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Myosin-Light-Chain Kinase/*chemistry ; Oligopeptides/genetics/metabolism ; Peptide Fragments ; Peptides/genetics/metabolism ; Protein Binding/physiology ; Protein Kinases/chemistry ; Sequence Alignment ; Sequence Homology
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-09-18
    Description: Structural models for the nitrogenase FeMo-cofactor and P-clusters are proposed based on crystallographic analysis of the nitrogenase molybdenum-iron (MoFe)-protein from Azotobacter vinelandii at 2.7 angstrom resolution. Each center consists of two bridged clusters; the FeMo-cofactor has 4Fe:3S and 1Mo:3Fe:3S clusters bridged by three non-protein ligands, and the P-clusters contain two 4Fe:4S clusters bridged by two cysteine thiol ligands. Six of the seven Fe sites in the FeMo-cofactor appear to have trigonal coordination geometry, including one ligand provided by a bridging group. The remaining Fe site has tetrahedral geometry and is liganded to the side chain of Cys alpha 275. The Mo site exhibits approximate octahedral coordination geometry and is liganded by three sulfurs in the cofactor, two oxygens from homocitrate, and the imidazole side chain of His alpha 442. The P-clusters are liganded by six cysteine thiol groups, two which bridge the two clusters, alpha 88 and beta 95, and four which singly coordinate the remaining Fe sites, alpha 62, alpha 154, beta 70, and beta 153. The side chain of Ser beta 188 may also coordinate one iron. The polypeptide folds of the homologous alpha and beta subunits surrounding the P-clusters are approximately related by a twofold rotation that may be utilized in the binding interactions between the MoFe-protein and the nitrogenase Fe-protein. Neither the FeMo-cofactor nor the P-clusters are exposed to the surface, suggesting that substrate entry, electron transfer, and product release must involve a carefully regulated sequence of interactions between the MoFe-protein and Fe-protein of nitrogenase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, J -- Rees, D C -- New York, N.Y. -- Science. 1992 Sep 18;257(5077):1677-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1529354" target="_blank"〉PubMed〈/a〉
    Keywords: Azotobacter vinelandii/*enzymology ; Binding Sites ; Chemistry, Physical ; Crystallization ; Electron Transport ; Iron-Sulfur Proteins/chemistry ; Macromolecular Substances ; *Models, Molecular ; Molecular Structure ; Molybdoferredoxin/*chemistry ; Nitrogen/metabolism ; Nitrogenase/*chemistry ; Oxidation-Reduction ; Physicochemical Phenomena ; Spectrum Analysis ; X-Ray Diffraction
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, K S -- Le, J -- New York, N.Y. -- Science. 1992 Dec 4;258(5088):1562-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1455239" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Escherichia coli/*drug effects/growth & development/pathogenicity ; Humans ; Interleukin-1/*pharmacology ; Virulence
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  • 42
    Publication Date: 1992-05-29
    Description: Transcriptional regulation of the bacteriophage T4 late genes requires the participation of three DNA polymerase accessory proteins that are encoded by T4 genes 44, 62, and 45, and that act at an enhancer-like site. Transcriptional activation by these DNA replication proteins also requires the function of an RNA polymerase-bound coactivator protein that is encoded by T4 gene 33 and a promoter recognition protein that is encoded by T4 gene 55. Transcriptional activation in DNA constructs, in which the enhancer and a T4 late promoter can be segregated on two rings of a DNA catenane, has now been analyzed. The ability of an interposed DNA-binding protein to affect communication between the enhancer and the promoter was also examined. Together, these experiments demonstrate that this transcription-activating signal is conveyed between its enhancer and a T4 late promoter by a DNA-tracking mechanism. Alternative activation mechanisms relying entirely on through-space interactions of enhancer-bound and promoter-bound proteins are excluded.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herendeen, D R -- Kassavetis, G A -- Geiduschek, E P -- New York, N.Y. -- Science. 1992 May 29;256(5061):1298-303.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, San Diego, La Jolla 92093-0634.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1598572" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; DNA Replication ; DNA, Viral/*genetics/metabolism ; DNA-Directed DNA Polymerase/metabolism ; Deoxyribonuclease EcoRI/genetics/metabolism ; *Enhancer Elements, Genetic ; Escherichia coli/*genetics ; Gene Expression Regulation, Viral ; *Genes, Viral ; Models, Genetic ; Plasmids ; Restriction Mapping ; T-Phages/*genetics ; *Trans-Activators ; *Transcription, Genetic ; Transcriptional Activation ; Viral Proteins/genetics/*metabolism
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  • 43
    Publication Date: 1992-04-17
    Description: Max is a basic-helix-loop-helix-leucine zipper protein capable of forming sequence-specific DNA binding complexes with Myc proteins. An alternatively spliced messenger RNA has been identified that encodes a form of Max truncated at the COOH-terminus. This delta Max protein retained the ability to bind to the CACGTG motif in a complex with c-Myc but lacks the nuclear localization signal and the putative regulatory domain of Max. When tested in a myc-ras cotransformation assay in rat embryo fibroblasts, Max suppressed, whereas delta Max enhanced, transformation. Thus, the max gene may encode both a negative and a positive regulator of c-Myc function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Makela, T P -- Koskinen, P J -- Vastrik, I -- Alitalo, K -- New York, N.Y. -- Science. 1992 Apr 17;256(5055):373-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Virology, University of Helsinki, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1566084" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Basic-Leucine Zipper Transcription Factors ; Binding Sites ; Cell Nucleus/metabolism ; Cell Transformation, Neoplastic/*drug effects/genetics ; DNA/chemistry/metabolism ; DNA-Binding Proteins/genetics/metabolism/*pharmacology ; Fibroblasts ; *Genes, myc ; *Genes, ras ; Humans ; Immunosorbent Techniques ; Molecular Sequence Data ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; RNA Splicing ; RNA, Messenger/genetics ; Rats ; Structure-Activity Relationship ; *Transcription Factors ; Transfection
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  • 44
    Publication Date: 1992-12-11
    Description: Class II major histocompatibility complexes bind peptides in an endosome-like compartment. When the class II null cell line 721.174 was transfected with class II DR3 genes, DR molecules were produced in normal amounts. However, the DR molecules were abnormally conformed and unstable because deletion of an antigen-processing gene had impaired intracellular formation of most class II-peptide complexes. Yet, 70 percent of the DR molecules still bore peptides, 80 percent of which were 21- to 24-amino acid fragments of the class II-associated invariant chain. These peptides were rare on DR3 from control cells. Thus, a defect in the main antigen-processing pathway revealed a process in which DR molecules bind long peptides derived from proteins present in the same compartment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sette, A -- Ceman, S -- Kubo, R T -- Sakaguchi, K -- Appella, E -- Hunt, D F -- Davis, T A -- Michel, H -- Shabanowitz, J -- Rudersdorf, R -- AI15486/AI/NIAID NIH HHS/ -- AI18634/AI/NIAID NIH HHS/ -- GM37537/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1801-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, University of Wisconsin, Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1465617" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Cell Line ; Gene Deletion ; *Genes, MHC Class II ; HLA-DR Antigens/*genetics/*metabolism ; HLA-DR3 Antigen/*genetics/metabolism ; Humans ; Kinetics ; Macromolecular Substances ; Molecular Sequence Data ; Peptides/*metabolism ; Transfection
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  • 45
    Publication Date: 1992-05-15
    Description: The basic helix-loop-helix (bHLH) protein MyoD is a transcription factor that is important for the induction of the myogenic phenotype. The DNA binding basic region (13 amino acids) is necessary for recognition of the consensus MyoD binding site, for transcriptional activation, and for conversion of fibroblasts to muscle. In contrast, the non-tissue-specific bHLH protein E12 can bind to the MyoD binding site but does not induce myogenesis. Here, it is shown that only two amino acids in the MyoD basic region and a single amino acid from the junction, which separates the basic region and helix 1, are sufficient for myogenic specificity when substituted into the corresponding region of E12. These findings suggest that the recognition of particular determinants in the basic region is required for conversion of fibroblasts to muscle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, R L -- Weintraub, H -- New York, N.Y. -- Science. 1992 May 15;256(5059):1027-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute Laboratory, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1317057" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Cell Differentiation ; Cell Line ; DNA/metabolism ; DNA Probes ; DNA-Binding Proteins/chemistry/metabolism/pharmacology ; Fibroblasts/cytology ; Fluorescent Antibody Technique ; Molecular Sequence Data ; Muscle Proteins/chemistry/genetics/*physiology ; Muscles/*cytology ; MyoD Protein ; Protein Conformation ; Structure-Activity Relationship ; Transcription Factors/chemistry/metabolism/pharmacology ; Transfection
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  • 46
    Publication Date: 1992-12-11
    Description: Nematode trans-spliced leader (SL) RNAs are composed of two domains, an exon [the 22-nucleotide spliced leader] and a small nuclear RNA (snRNA)-like sequence. Participation in vitro of the spliced leader RNA in trans-splicing reactions is independent of the exon sequence or size and instead depends on features contained in the snRNA-like domain of the molecule. Chemical modification interference analysis has revealed that two short sequence elements in the snRNA-like domain are necessary for SL RNA activity. These elements are sufficient for such activity because when added to a 72-nucleotide fragment of a nematode U1 snRNA, this hybrid RNA could participate in trans-splicing reactions in vitro. One of the critical sequence elements may function by base-pairing with U6 snRNA, an essential U snRNA for both cis- and trans-splicing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hannon, G J -- Maroney, P A -- Yu, Y T -- Hannon, G E -- Nilsen, T W -- AI28799/AI/NIAID NIH HHS/ -- GM31528/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1775-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1465612" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ascaris/*genetics ; Base Sequence ; Binding Sites ; Exons ; Models, Structural ; Molecular Sequence Data ; Nucleic Acid Conformation ; *RNA Splicing ; RNA, Messenger/genetics/*metabolism ; RNA, Small Nuclear/chemistry/genetics/*metabolism
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  • 47
    Publication Date: 1992-07-03
    Description: The messenger RNAs of human immunodeficiency virus-1 (HIV-1) have an RNA hairpin structure, TAR, at their 5' ends that contains a six-nucleotide loop and a three-nucleotide bulge. The conformations of TAR RNA and of TAR with an arginine analog specifically bound at the binding site for the viral protein, Tat, were characterized by nuclear magnetic resonance (NMR) spectroscopy. Upon arginine binding, the bulge changes conformation, and essential nucleotides for binding, U23 and A27.U38, form a base-triple interaction that stabilizes arginine hydrogen bonding to G26 and phosphates. Specificity in the arginine-TAR interaction appears to be derived largely from the structure of the RNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Puglisi, J D -- Tan, R -- Calnan, B J -- Frankel, A D -- Williamson, J R -- AI29135/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1992 Jul 3;257(5066):76-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1621097" target="_blank"〉PubMed〈/a〉
    Keywords: Arginine/*metabolism ; Base Sequence ; Binding Sites ; Gene Products, tat/metabolism ; HIV-1/*genetics ; Hydrogen Bonding ; Magnetic Resonance Spectroscopy/methods ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Messenger/*chemistry/metabolism ; RNA, Viral/*chemistry/metabolism ; RNA-Binding Proteins/*chemistry/metabolism ; tat Gene Products, Human Immunodeficiency Virus
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  • 48
    Publication Date: 1992-02-21
    Description: A class of regulators of eukaryotic gene expression contains a conserved amino acid sequence responsible for protein oligomerization and binding to DNA. This structure consists of an arginine- and lysine-rich basic region followed by a helix-loop-helix motif, which together mediate specific binding to DNA. Peptides were prepared that span this motif in the MyoD protein; in solution, they formed alpha-helical dimers and tetramers. They bound to DNA as dimers and their alpha-helical content increased on binding. Parallel and antiparallel four-helix models of the DNA-bound dimer were constructed. Peptides containing disulfide bonds were engineered to test the correctness of the two models. A disulfide that is compatible with the parallel model promotes specific interaction with DNA, whereas a disulfide compatible with the antiparallel model abolishes specific binding. Electron paramagnetic resonance (EPR) measurements of nitroxide-labeled peptides provided intersubunit distance measurements that also supported the parallel model.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anthony-Cahill, S J -- Benfield, P A -- Fairman, R -- Wasserman, Z R -- Brenner, S L -- Stafford, W F 3rd -- Altenbach, C -- Hubbell, W L -- DeGrado, W F -- GM13731/GM/NIGMS NIH HHS/ -- GM14321/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Feb 21;255(5047):979-83.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biotechnology Department, DuPont Merck Pharmaceutical Co., Wilmington, DE 19880-0328.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1312255" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Circular Dichroism ; DNA-Binding Proteins/*chemistry ; Disulfides ; Electron Spin Resonance Spectroscopy ; Enhancer Elements, Genetic ; Gene Expression Regulation ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Regulatory Sequences, Nucleic Acid ; Sequence Alignment ; Transcription Factors/*chemistry
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  • 49
    Publication Date: 1992-08-21
    Description: Pit-1 is a pituitary-specific transcription factor responsible for pituitary development and hormone expression in mammals. Mutations in the gene encoding Pit-1 have been found in two dwarf mouse strains displaying hypoplasia of growth hormone, prolactin, and thyroid-stimulating, hormone-secreting cell types in the anterior pituitary. A point mutation in this gene was identified on one allele in a patient with combined pituitary hormone deficiency. Mutant Pit-1 binds DNA normally but acts as a dominant inhibitor of Pit-1 action in the pituitary.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Radovick, S -- Nations, M -- Du, Y -- Berg, L A -- Weintraub, B D -- Wondisford, F E -- New York, N.Y. -- Science. 1992 Aug 21;257(5073):1115-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Rainbow Babies and Childrens Hospital, Cleveland, OH.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1509262" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Binding Sites ; DNA/chemistry/genetics/metabolism ; DNA-Binding Proteins/chemistry/*genetics ; Growth Hormone/deficiency/genetics ; Humans ; Molecular Sequence Data ; *Mutation ; Pituitary Gland, Anterior/metabolism/pathology ; Pituitary Hormones/*deficiency ; Polymerase Chain Reaction ; Prolactin/deficiency/genetics ; Promoter Regions, Genetic ; Thyrotropin/deficiency/genetics ; Transcription Factor Pit-1 ; Transcription Factors/chemistry/*genetics ; Transfection
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-24
    Description: The mammalian splicing factor SC35 is required for the first step in the splicing reaction and for spliceosome assembly. The cloning and characterization of a complementary DNA encoding this protein revealed that it is a member of a family of splicing factors that includes mammalian SF2/ASF. This family of proteins is characterized by the presence of a ribonucleoprotein (RNP)-type RNA binding motif and a carboxyl-terminal serine-arginine-rich (SR) domain. A search of the DNA sequence database revealed that the thymus-specific exon (ET) of the c-myb proto-oncogene is encoded on the antisense strand of the SC35 gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fu, X D -- Maniatis, T -- GM42231/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 24;256(5056):535-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1373910" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Baculoviridae/genetics ; Base Sequence ; Binding Sites ; Blotting, Northern ; Cell Line ; Cloning, Molecular ; Codon ; DNA/chemistry/*isolation & purification ; Exons ; Humans ; Molecular Sequence Data ; *Nuclear Proteins ; Proteins/chemistry/*genetics ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-myb ; RNA/metabolism ; *RNA Splicing ; *Ribonucleoproteins ; Sequence Homology, Nucleic Acid ; Transfection
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  • 51
    Publication Date: 1992-03-13
    Description: Introns have generally been assumed to be passive in the transfer RNA splicing reaction. Experiments have now been done showing that the endonuclease is able to cut a precursor provided that a base in the single-stranded loop of the intron can pair with the base of the 5' exon situated at the position that immediately follows the anticodon stem (position 33 in the yeast tRNA isoacceptor pre-tRNA(Leu)3, position 32 in yeast pre-tRNA(Phe)). The elucidation of the role of the intron reveals that in addition to the conserved bases, there are positions in the mature domain which, although not necessarily occupied by the same base in all pre-tRNA's, nevertheless have a fundamental role in the splicing reaction. These positions are termed cardinal positions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldi, M I -- Mattoccia, E -- Bufardeci, E -- Fabbri, S -- Tocchini-Valentini, G P -- New York, N.Y. -- Science. 1992 Mar 13;255(5050):1404-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Cell Biology, Consiglio Nazionale delle Ricerche, Roma, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1542788" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Endoribonucleases/*metabolism ; Exons/physiology ; Introns/*physiology ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; RNA Precursors/chemistry/*metabolism ; RNA Splicing/*physiology ; RNA, Transfer/chemistry/*metabolism ; RNA, Transfer, Leu/metabolism ; RNA, Transfer, Phe/metabolism ; Xenopus laevis
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  • 52
    Publication Date: 1992-08-14
    Description: The x-ray structures of a murine MHC class I molecule (H-2Kb) were determined in complex with two different viral peptides, derived from the vesicular stomatitis virus nucleoprotein (52-59), VSV-8, and the Sendai virus nucleoprotein (324-332), SEV-9. The H-2Kb complexes were refined at 2.3 A for VSV-8 and 2.5 A for SEV-9. The structure of H-2Kb exhibits a high degree of similarity with human HLA class I, although the individual domains can have slightly altered dispositions. Both peptides bind in extended conformations with most of their surfaces buried in the H-2Kb binding groove. The nonamer peptide maintains the same amino- and carboxyl-terminal interactions as the octamer primarily by the insertion of a bulge in the center of an otherwise beta conformation. Most of the specific interactions are between side-chain atoms of H-2Kb and main-chain atoms of peptide. This binding scheme accounts in large part for the enormous diversity of peptide sequences that bind with high affinity to class I molecules. Small but significant conformational changes in H-2Kb are associated with peptide binding, and these synergistic movements may be an integral part of the T cell receptor recognition process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fremont, D H -- Matsumura, M -- Stura, E A -- Peterson, P A -- Wilson, I A -- CA-09523/CA/NCI NIH HHS/ -- CA-97489/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):919-27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1323877" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; H-2 Antigens/*chemistry/metabolism ; Mice ; Models, Molecular ; Molecular Sequence Data ; Parainfluenza Virus 1, Human/metabolism ; Protein Binding ; Protein Conformation ; Solvents ; Vesicular stomatitis Indiana virus/metabolism ; Viral Proteins/*chemistry/metabolism ; X-Ray Diffraction
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-01-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoffman, M -- New York, N.Y. -- Science. 1992 Jan 10;255(5041):159.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1553541" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; GTP Phosphohydrolases/*metabolism ; GTPase-Activating Proteins ; Proteins/*metabolism ; Signal Transduction ; ras GTPase-Activating Proteins
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  • 54
    Publication Date: 1992-08-14
    Description: The peptide binding cleft of the class I human histocompatibility antigen, HLA-A2, contains conserved amino acid residues clustered in the two ends of the cleft in pockets A and F as well as polymorphic residues. The function of two conserved tyrosines in the A pocket was investigated by mutating them to phenylalanines and of a conserved tyrosine and threonine in the F pocket by mutating them to phenylalanine and valine, respectively. Presentation of influenza virus peptides and of intact virus to cytolytic T lymphocytes (CTLs) was then examined. The magnitude of the reduction seen by the mutation of the two tyrosines in the A pocket suggests that hydrogen bonds involving them have a critical function in the binding of the NH2-terminal NH3+ of the peptide nonamer and possibly of all bound peptide nonamers. In contrast, the mutations in the F pocket had no effect on CTL recognition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Latron, F -- Pazmany, L -- Morrison, J -- Moots, R -- Saper, M A -- McMichael, A -- Strominger, J L -- AI 20182/AI/NIAID NIH HHS/ -- CA 47554/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):964-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1380181" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology ; Binding Sites ; Cell Line ; Cloning, Molecular ; Epitopes/immunology/metabolism ; HLA-A2 Antigen/chemistry/genetics/*metabolism ; Influenza A virus ; Kinetics ; Models, Molecular ; Mutagenesis, Site-Directed ; Oligopeptides/immunology/*metabolism ; Protein Conformation ; Recombinant Proteins/chemistry/metabolism ; T-Lymphocytes, Cytotoxic/*immunology ; Transfection ; Viral Proteins/metabolism
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  • 55
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-04-10
    Description: Positive control of the sex-specific alternative splicing of doublesex (dsx) precursor messenger RNA (pre-mRNA) in Drosophila melanogaster involves the activation of a female-specific 3' splice site by the products of the transformer (tra) and transformer-2 (tra-2) genes. The mechanisms of this process were investigated in an in vitro system in which the female-specific 3' splice site could be activated by recombinant Tra or Tra-2 (or both). An exon sequence essential for regulation in vivo was shown to be both necessary and sufficient for activation in vitro. Nuclear proteins in addition to Tra and Tra-2 were found to bind specifically to this exon sequence. Therefore, Tra and Tra-2 may act by promoting the assembly of a multiprotein complex on the exon sequence. This complex may facilitate recognition of the adjacent 3' splice site by the splicing machinery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tian, M -- Maniatis, T -- GM42231/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Apr 10;256(5054):237-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1566072" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Baculoviridae/genetics ; Binding Sites ; Cell Nucleus/metabolism ; Cloning, Molecular ; *Drosophila Proteins ; Drosophila melanogaster/*genetics ; Exons ; Female ; Globins/genetics ; HeLa Cells ; Humans ; Male ; Nuclear Proteins/genetics/*metabolism ; RNA Precursors/*genetics ; *RNA Splicing ; Recombinant Proteins/metabolism ; Ribonucleoproteins/genetics/*metabolism ; Sex Characteristics ; Transcription, Genetic
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  • 56
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-05-15
    Description: A simple and efficient method for synthesizing long, site-specifically modified RNA molecules was developed whereby segments of RNA were joined with the use of bacteriophage T4 DNA ligase. A single hydrogen or O-methyl group was substituted for the 2'-hydroxyl group at either splice site of a nuclear pre-messenger RNA substrate. Splicing of the modified pre-messenger RNA's in vitro revealed that, although a 2'-hydroxyl is not absolutely required at either splice site, the 2'-hydroxyl at the 3' splice site is important for the second step of splicing. These results are compared to previous studies of analogous 2'-hydroxyl groups in the self-splicing Tetrahymena group I intron.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, M J -- Sharp, P A -- P30-CA14051/CA/NCI NIH HHS/ -- R01 GM34277/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 May 15;256(5059):992-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1589782" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; DNA Ligases/metabolism ; DNA-Directed RNA Polymerases/metabolism ; Exons ; Introns ; Kinetics ; Molecular Sequence Data ; RNA Precursors/*chemistry/metabolism ; *RNA Splicing ; RNA, Messenger/*chemistry/metabolism ; Structure-Activity Relationship ; Tetrahymena/genetics ; Viral Proteins
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  • 57
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-09-18
    Description: To explore the underlying mechanisms by which genes are regulated in eukaryotes, long-distance transcriptional activation and threshold effects were reconstituted in vitro. Long-range activation of transcription by GAL4-VP16 protein located 1300 base pairs upstream of the RNA start site was dependent on packaging of the template into histone H1-containing chromatin. A transcriptional threshold effect by GAL4-VP16 was observed with repressed chromatin templates but not naked DNA templates. The experimental data with the chromatin templates were similar to the theoretical activation profile that is predicted if the action of each DNA bound protomer of GAL4-VP16 were independent and additive in terms of free energy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laybourn, P J -- Kadonaga, J T -- New York, N.Y. -- Science. 1992 Sep 18;257(5077):1682-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, San Diego, La Jolla 92093.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1388287" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus Early Proteins ; Binding Sites ; Chromatin/metabolism ; DNA/metabolism ; Fungal Proteins/metabolism/pharmacology ; Oncogene Proteins, Viral/genetics ; Promoter Regions, Genetic/genetics ; RNA Polymerase II/*metabolism ; Sp1 Transcription Factor/pharmacology ; Templates, Genetic ; Trans-Activators/metabolism/pharmacology ; Transcription Factors/metabolism/pharmacology ; *Transcription, Genetic/drug effects
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  • 58
    Publication Date: 1992-06-05
    Description: The phagocyte respiratory burst oxidase is a flavin-adenine dinucleotide (FAD)-dependent dehydrogenase and an electron transferase that reduces molecular oxygen to superoxide anion, a precursor of microbicidal oxidants. Several proteins required for assembly of the oxidase have been characterized, but the identity of its flavin-binding component has been unclear. Oxidase activity was reconstituted in vitro with only the purified oxidase proteins p47phox, p67phox, Rac-related guanine nucleotide (GTP)-binding proteins, and membrane-bound cytochrome b558. The reconstituted oxidase required added FAD, and FAD binding was localized to cytochrome b558. Alignment of the amino acid sequence of the beta subunit of cytochrome b558 (gp91phox) with other flavoproteins revealed similarities to the nicotinamide adenine dinucleotide phosphate (reduced) (NADPH)-binding domains. Thus flavocytochrome b558 is the only obligate electron transporting component of the NADPH oxidase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rotrosen, D -- Yeung, C L -- Leto, T L -- Malech, H L -- Kwong, C H -- New York, N.Y. -- Science. 1992 Jun 5;256(5062):1459-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1318579" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cell Line ; Cell-Free System ; Cytochrome b Group/*blood/genetics/isolation & purification ; Ferredoxin-NADP Reductase/genetics/metabolism ; Humans ; Insects ; Molecular Sequence Data ; NADH, NADPH Oxidoreductases/*blood/genetics/isolation & purification ; NADP/metabolism ; NADPH Oxidase ; Neutrophils/*enzymology ; Phagocytes/*enzymology ; Plants/enzymology ; Recombinant Proteins/chemistry/metabolism ; Sequence Homology, Nucleic Acid ; Superoxides/blood ; Transfection
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  • 59
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-07-31
    Description: The location of the bound lipid in the soluble lipoprotein lipovitellin has been determined by neutron crystallographic techniques. With the use of the contrast variation method, whereby the crystals are soaked in different H2O-D2O mixtures, the lipid has been found to occupy a large cavity in the protein whose structure had previously been determined by x-ray crystallography. The lipid appears to be bound in the form of a bilayer with the major protein-lipid interactions being hydrophobic and with the lipid headgroups projecting into the bulk solvent and into a solvent-filled space in the cavity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Timmins, P A -- Poliks, B -- Banaszak, L -- New York, N.Y. -- Science. 1992 Jul 31;257(5070):652-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Laue-Langevin, Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1496377" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Chemistry, Physical ; Crystallography ; Deuterium ; Egg Proteins ; Egg Proteins, Dietary/*chemistry/metabolism ; *Lipid Metabolism ; Lipids/analysis ; Macromolecular Substances ; Molecular Structure ; Neutrons ; Physicochemical Phenomena ; Protein Conformation ; Water ; X-Ray Diffraction
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  • 60
    Publication Date: 1992-12-04
    Description: Phthalate dioxygenase reductase (PDR) is a prototypical iron-sulfur flavoprotein (36 kilodaltons) that utilizes flavin mononucleotide (FMN) to mediate electron transfer from the two-electron donor, reduced nicotinamide adenine nucleotide (NADH), to the one-electron acceptor, [2Fe-2S]. The crystal structure of oxidized PDR from Pseudomonas cepacia has been analyzed at 2.0 angstrom resolution resolution; reduced PDR and pyridine nucleotide complexes have been analyzed at 2.7 angstrom resolution. NADH, FMN, and the [2Fe-2S] cluster, bound to distinct domains, are brought together near a central cleft in the molecule, with only 4.9 angstroms separating the flavin 8-methyl and a cysteine sulfur ligated to iron. The domains that bind FMN and [2Fe-2S] are packed so that the flavin ring and the plane of the [2Fe-2S] core are approximately perpendicular. The [2Fe-2S] group is bound by four cysteines in a site resembling that in plant ferredoxins, but its redox potential (-174 millivolts at pH 7.0) is much higher than the potentials of plant ferredoxins. Structural and sequence similarities assign PDR to a distinct family of flavoprotein reductases, all related to ferredoxin NADP(+)-reductase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Correll, C C -- Batie, C J -- Ballou, D P -- Ludwig, M L -- GM 16429/GM/NIGMS NIH HHS/ -- GM 20877/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Dec 4;258(5088):1604-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Biophysics, University of Michigan, Ann Arbor 48109.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1280857" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Burkholderia cepacia/enzymology ; Electron Transport ; Flavin Mononucleotide/*metabolism ; Iron-Sulfur Proteins/*chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; NAD/*metabolism ; Oxidoreductases/*chemistry/metabolism ; *Protein Conformation ; *Protein Structure, Secondary ; Sequence Homology, Amino Acid
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  • 61
    Publication Date: 1992-09-18
    Description: The nitrogenase enzyme system catalyzes the ATP (adenosine triphosphate)-dependent reduction of dinitrogen to ammonia during the process of nitrogen fixation. Nitrogenase consists of two proteins: the iron (Fe)-protein, which couples hydrolysis of ATP to electron transfer, and the molybdenum-iron (MoFe)-protein, which contains the dinitrogen binding site. In order to address the role of ATP in nitrogen fixation, the crystal structure of the nitrogenase Fe-protein from Azotobacter vinelandii has been determined at 2.9 angstrom (A) resolution. Fe-protein is a dimer of two identical subunits that coordinate a single 4Fe:4S cluster. Each subunit folds as a single alpha/beta type domain, which together symmetrically ligate the surface exposed 4Fe:4S cluster through two cysteines from each subunit. A single bound ADP (adenosine diphosphate) molecule is located in the interface region between the two subunits. Because the phosphate groups of this nucleotide are approximately 20 A from the 4Fe:4S cluster, it is unlikely that ATP hydrolysis and electron transfer are directly coupled. Instead, it appears that interactions between the nucleotide and cluster sites must be indirectly coupled by allosteric changes occurring at the subunit interface. The coupling between protein conformation and nucleotide hydrolysis in Fe-protein exhibits general similarities to the H-Ras p21 and recA proteins that have been recently characterized structurally. The Fe-protein structure may be relevant to the functioning of other biochemical energy-transducing systems containing two nucleotide-binding sites, including membrane transport proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Georgiadis, M M -- Komiya, H -- Chakrabarti, P -- Woo, D -- Kornuc, J J -- Rees, D C -- GM45162/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1992 Sep 18;257(5077):1653-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1529353" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism/pharmacology ; Amino Acid Sequence ; Azotobacter vinelandii/*enzymology ; Binding Sites ; Chemistry, Physical ; Crystallization ; Electron Transport ; Hydrolysis ; Iron-Sulfur Proteins/*chemistry ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Molybdoferredoxin/chemistry ; Nitrogenase/*chemistry/metabolism ; Physicochemical Phenomena ; Protein Conformation ; X-Ray Diffraction
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-08-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):880-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1502554" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Histocompatibility Antigens Class I/*chemistry/metabolism ; Humans ; Hydrogen Bonding ; Major Histocompatibility Complex ; Models, Molecular ; Protein Binding ; Protein Conformation ; Proteins/chemistry/metabolism ; T-Lymphocytes/immunology
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  • 63
    Publication Date: 1992-04-17
    Description: Transcription factor NF-kappa B comprises two proteins, p50 and p65, that have sequence similarity to the v-rel oncogene. In primary hematopoietic cell populations an alternatively spliced form of NF-kappa B p65 mRNA was observed that encoded a protein designated p65 delta. Expression of the p65 delta cDNA in Rat-1 fibroblasts resulted in focus formation, anchorage-independent growth in soft agar, and tumor formation in athymic nude mice, effects not obtained with expression of p65 or a p65 delta mutant that contains a disruption within the transcriptional activation domain. Thus, p65 delta, which associated weakly and interfered with DNA binding by p65, may sequester an essential limiting regulatory factor or factors required for NF-kappa B function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narayanan, R -- Klement, J F -- Ruben, S M -- Higgins, K A -- Rosen, C A -- New York, N.Y. -- Science. 1992 Apr 17;256(5055):367-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, Hoffmann-LaRoche, Inc., Nutley, NJ 07110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1566083" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Cell Transformation, Neoplastic/*genetics ; DNA/genetics/metabolism ; Fibroblasts/metabolism ; *Genetic Variation ; Hematopoietic Stem Cells/chemistry ; Humans ; Mice ; Mice, Nude ; Molecular Sequence Data ; NF-kappa B/*genetics ; Neoplasm Transplantation ; Oncogene Proteins v-rel ; Polymerase Chain Reaction ; RNA Splicing ; RNA, Messenger/analysis/genetics ; Rats ; Retroviridae Proteins, Oncogenic/genetics ; Transfection
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-10-16
    Description: The cellular transcription factor E2F, previously identified as a component of early adenovirus transcription, has now been shown to be important in cell proliferation control. E2F appears to be a functional target for the action of the tumor suppressor protein Rb that is encoded by the retinoblastoma susceptibility gene. The disruption of this E2F-Rb interaction, as well as a complex involving E2F in association with the cell cycle-regulated cyclin A-cdk2 kinase complex, may be a common mechanism of action for the oncoproteins encoded by the DNA tumor viruses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nevins, J R -- New York, N.Y. -- Science. 1992 Oct 16;258(5081):424-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Section of Genetics, Duke University Medical Center, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1411535" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus E1A Proteins/metabolism ; Adenoviruses, Human/genetics ; Binding Sites ; *Carrier Proteins ; Cell Cycle ; *Cell Cycle Proteins ; *Cell Transformation, Viral ; Cloning, Molecular ; DNA-Binding Proteins/metabolism ; E2F Transcription Factors ; *Gene Expression Regulation, Viral ; Genes, Tumor Suppressor ; Humans ; Oncogene Proteins, Viral/*metabolism ; Protein Binding ; Regulatory Sequences, Nucleic Acid ; Retinoblastoma Protein/*metabolism ; Retinoblastoma-Binding Protein 1 ; Transcription Factor DP1 ; Transcription Factors/*metabolism
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  • 65
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1992-08-14
    Description: Effective methods are needed to identify and isolate those genes that are differentially expressed in various cells or under altered conditions. This report describes a method to separate and clone individual messenger RNAs (mRNAs) by means of the polymerase chain reaction. The key element is to use a set of oligonucleotide primers, one being anchored to the polyadenylate tail of a subset of mRNAs, the other being short and arbitrary in sequence so that it anneals at different positions relative to the first primer. The mRNA subpopulations defined by these primer pairs were amplified after reverse transcription and resolved on a DNA sequencing gel. When multiple primer sets were used, reproducible patterns of amplified complementary DNA fragments were obtained that showed strong dependence on sequence specificity of either primer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liang, P -- Pardee, A B -- New York, N.Y. -- Science. 1992 Aug 14;257(5072):967-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1354393" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Breast Neoplasms/genetics ; Cloning, Molecular/methods ; DNA/genetics ; Humans ; Molecular Sequence Data ; Neoplasm Metastasis ; Nucleoside-Phosphate Kinase/genetics ; Oligodeoxyribonucleotides ; Poly A/genetics ; Polymerase Chain Reaction/*methods ; RNA, Messenger/biosynthesis/*genetics ; Templates, Genetic
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  • 66
    Publication Date: 1992-05-01
    Description: The three-dimensional solution structure of the complex between calcium-bound calmodulin (Ca(2+)-CaM) and a 26-residue synthetic peptide comprising the CaM binding domain (residues 577 to 602) of skeletal muscle myosin light chain kinase, has been determined using multidimensional heteronuclear filtered and separated nuclear magnetic resonance spectroscopy. The two domains of CaM (residues 6 to 73 and 83 to 146) remain essentially unchanged upon complexation. The long central helix (residues 65 to 93), however, which connects the two domains in the crystal structure of Ca(2+)-CaM, is disrupted into two helices connected by a long flexible loop (residues 74 to 82), thereby enabling the two domains to clamp residues 3 to 21 of the bound peptide, which adopt a helical conformation. The overall structure of the complex is globular, approximating an ellipsoid of dimensions 47 by 32 by 30 angstroms. The helical peptide is located in a hydrophobic channel that passes through the center of the ellipsoid at an angle of approximately 45 degrees with its long axis. The complex is mainly stabilized by hydrophobic interactions which, from the CaM side, involve an unusually large number of methionines. Key residues of the peptide are Trp4 and Phe17, which serve to anchor the amino- and carboxyl-terminal halves of the peptide to the carboxyl- and amino-terminal domains of CaM, respectively. Sequence comparisons indicate that a number of peptides that bind CaM with high affinity share this common feature containing either aromatic residues or long-chain hydrophobic ones separated by a stretch of 12 residues, suggesting that they interact with CaM in a similar manner.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ikura, M -- Clore, G M -- Gronenborn, A M -- Zhu, G -- Klee, C B -- Bax, A -- New York, N.Y. -- Science. 1992 May 1;256(5057):632-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1585175" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Calcium/metabolism ; Calmodulin/*chemistry/metabolism ; Drosophila melanogaster ; Hydrogen Bonding ; *Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Muscles/enzymology ; Myosin-Light-Chain Kinase/chemistry/metabolism ; Peptide Fragments/*chemistry/metabolism ; Protein Conformation ; Rabbits
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  • 67
    Publication Date: 1990-08-17
    Description: The transcription factor C/EBP uses a bipartite structural motif to bind DNA. Two protein chains dimerize through a set of amphipathic alpha helices termed the leucine zipper. Highly basic polypeptide regions emerge from the zipper to form a linked set of DNA contact surfaces. In the recently proposed a "scissors grip" model, the paired set of basic regions begin DNA contact at a central point and track in opposite directions along the major groove, forming a molecular clamp around DNA. This model predicts that C/EBP must undertake significant changes in protein conformation as it binds and releases DNA. The basic region of ligand-free C/EBP is highly sensitive to protease digestion. Pronounced resistance to proteolysis occurred when C/EBP associated with its specific DNA substrate. Sequencing of discrete proteolytic fragments showed that prominent sites for proteolysis occur at two junction points predicted by the "scissors grip" model. One junction corresponds to the cleft where the basic regions emerge from the leucine zipper. The other corresponds to a localized nonhelical segment that has been hypothesized to contain an N-cap and facilitate the sharp angulation necessary for the basic region to track continuously in the major groove of DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shuman, J D -- Vinson, C R -- McKnight, S L -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):771-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Research Laboratories, Department of Embryology, Baltimore, MD 21210.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2202050" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; CCAAT-Enhancer-Binding Proteins ; Chromatography, High Pressure Liquid ; DNA/*metabolism ; DNA-Binding Proteins/metabolism ; Kinetics ; Leucine ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Nuclear Proteins/*metabolism ; Peptide Fragments/metabolism ; Peptide Hydrolases/*metabolism ; Protein Conformation ; Transcription Factors/*metabolism ; Trypsin/metabolism
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  • 68
    Publication Date: 1990-07-06
    Description: Oligonucleotides equipped with EDTA-Fe can bind specifically to duplex DNA by triple-helix formation and produce double-strand cleavage at binding sites greater than 12 base pairs in size. To demonstrate that oligonucleotide-directed triple-helix formation is a viable chemical approach for the site-specific cleavage of large genomic DNA, an oligonucleotide with EDTA-Fe at the 5' and 3' ends was targeted to a 20-base pair sequence in the 340-kilobase pair chromosome III of Saccharomyces cerevisiae. Double-strand cleavage products of the correct size and location were observed, indicating that the oligonucleotide bound and cleaved the target site among almost 14 megabase pairs of DNA. Because oligonucleotide-directed triple-helix formation has the potential to be a general solution for DNA recognition, this result has implications for physical mapping of chromosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Strobel, S A -- Dervan, P B -- GM 42966/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Jul 6;249(4964):73-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2195655" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Chromosomes, Fungal/*metabolism ; DNA, Fungal/*genetics/metabolism ; Densitometry ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; Nucleic Acid Conformation ; Nucleic Acid Hybridization ; Oligonucleotides/*genetics/metabolism ; Saccharomyces cerevisiae/*genetics
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  • 69
    Publication Date: 1990-05-18
    Description: Most proteins destined for export from Escherichia coli are made as precursors containing amino-terminal leader sequences that are essential for export and that are removed during the process. The initial step in export of a subset of proteins, which includes maltose-binding protein, is binding of the precursor by the molecular chaperone SecB. This work shows directly that SecB binds with high affinity to unfolded maltose-binding protein but does not specifically recognize and bind the leader. Rather, the leader modulates folding to expose elements in the remainder of the polypeptide that are recognized by SecB.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Randall, L L -- Topping, T B -- Hardy, S J -- GM 29798/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 May 18;248(4957):860-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemistry/Biophysics Program, Washington State University, Pullman 99164-4660.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2188362" target="_blank"〉PubMed〈/a〉
    Keywords: *ATP-Binding Cassette Transporters ; Bacterial Proteins/*metabolism ; Binding Sites ; Biological Transport ; Carrier Proteins/*metabolism ; Cytosol/metabolism ; Escherichia coli/*metabolism ; *Escherichia coli Proteins ; Maltose-Binding Proteins ; Molecular Weight ; *Monosaccharide Transport Proteins ; Protein Conformation ; Protein Precursors/*metabolism ; Protein Sorting Signals/*metabolism
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-04-27
    Description: Light-dependent expression of rbcS, the gene encoding the small subunit of ribulose-1,5-bisphosphate carboxylase, which is the key enzyme involved in carbon fixation in higher plants, is regulated at the transcriptional level. Sequence analysis of the gene has uncovered a conserved GT motif in the -150 to -100 region of many rbcS promoters. This motif serves as the binding site of a nuclear factor, designated GT-1. Analysis of site-specific mutants of pea rbcS-3A promoter demonstrated that GT-1 binding in vitro is correlated with light-responsive expression of the rbcS promoter in transgenic plants. However, it is not known whether factors other than GT-1 might also be required for activation of transcription by light. A synthetic tetramer of box II (TGTGTGGTTAATATG), the GT-1 binding site located between -152 to -138 of the rbcS-3A promoter, inserted upstream of a truncated cauliflower mosaic virus 35S promoter is sufficient to confer expression in leaves of transgenic tobacco. This expression occurs principally in chloroplast-containing cells, is induced by light, and is correlated with the ability of box II to bind GT-1 in vitro. The data show that the binding site for GT-1 is likely to be a part of the molecular light switch for rbcS activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lam, E -- Chua, N H -- New York, N.Y. -- Science. 1990 Apr 27;248(4954):471-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Plant Molecular Biology, Rockefeller University, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2330508" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Chloramphenicol O-Acetyltransferase/genetics ; Cloning, Molecular ; DNA-Binding Proteins/*metabolism ; Gene Expression Regulation/*physiology ; Genetic Vectors ; *Light ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/*metabolism ; Plant Proteins/*metabolism ; *Plants, Toxic ; Promoter Regions, Genetic/genetics ; Ribulose-Bisphosphate Carboxylase/*genetics ; Tobacco/enzymology/*genetics ; Transcription, Genetic/radiation effects ; Transformation, Genetic
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-02-09
    Description: Transcription of a typical eukaryotic gene by RNA polymerase II is activated by proteins bound to sites found near the beginning of the gene as well as to sites, called enhancers, located a great distance from the gene. According to one view, the primary difference between an activator that can work at a large distance and one that cannot is that the former bears a particularly strong activating region; the stronger the activating region, the more readily the activator interacts with its target bound near the transcriptional start site, with the intervening DNA looping out to accommodate the reaction. One alternative view is that the effect of proteins bound to enhancers might require some special aspect of cellular or chromosome structure. Consistent with the first view, an activator bearing an unusually potent activating region can stimulate transcription of a mammalian gene in a HeLa nuclear extract when bound as far as 1.3 kilobase pairs upstream or 320 base pairs downstream of the transcriptional start site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carey, M -- Leatherwood, J -- Ptashne, M -- New York, N.Y. -- Science. 1990 Feb 9;247(4943):710-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2405489" target="_blank"〉PubMed〈/a〉
    Keywords: Activating Transcription Factors ; Binding Sites ; Blood Proteins/pharmacology ; Cloning, Molecular ; DNA/metabolism ; DNA-Binding Proteins ; Fungal Proteins/metabolism/*pharmacology ; HeLa Cells ; Phosphoproteins/pharmacology ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; Recombinant Fusion Proteins/pharmacology ; *Saccharomyces cerevisiae Proteins ; Templates, Genetic ; Trans-Activators/pharmacology ; Transcription Factors/pharmacology ; Transcription, Genetic/*drug effects
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  • 72
    Publication Date: 1990-07-27
    Description: The major autophosphorylation sites of the rat beta II isozyme of protein kinase C were identified. The modified threonine and serine residues were found in the amino-terminal peptide, the carboxyl-terminal tail, and the hinge region between the regulatory lipid-binding domain and the catalytic kinase domain. Because this autophosphorylation follows an intrapeptide mechanism, extraordinary flexibility of the protein is necessary to phosphorylate the three regions. Comparison of the sequences surrounding the modified residues showed no obvious recognition motif nor any similarity to substrate phosphorylation sites, suggesting that proximity to the active site may be the primary criterion for their phosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flint, A J -- Paladini, R D -- Koshland, D E Jr -- DK09765/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1990 Jul 27;249(4967):408-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2377895" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Brain/enzymology ; Cloning, Molecular ; Isoenzymes/genetics/*metabolism ; Molecular Sequence Data ; Peptide Fragments/isolation & purification/metabolism ; Phosphorylation ; Protein Conformation ; Protein Kinase C/genetics/*metabolism ; Rats ; Recombinant Proteins/metabolism ; Signal Transduction ; Trypsin
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  • 73
    Publication Date: 1990-11-09
    Description: High sequence selectivity in DNA-protein interactions was analyzed by measuring discrimination by Eco RI endonuclease between the recognition site GAATTC and systematically altered DNA sites. Base analogue substitutions that preserve the sequence-dependent conformational motif of the GAATTC site permit deletion of single sites of protein-base contact at a cost of +1 to +2 kcal/mol. However, the introduction of any one incorrect natural base pair costs +6 to +13 kcal/mol in transition state interaction energy, the resultant of the following interdependent factors: deletion of one or two hydrogen bonds between the protein and a purine base; unfavourable steric apposition between a group on the protein and an incorrectly placed functional group on a base; disruption of a pyrimidine contact with the protein; loss of some crucial interactions between protein and DNA phosphates; and an increased energetic cost of attaining the required DNA conformation in the transition state complex. Eco RI endonuclease thus achieves stringent discrimination by both "direct readout" (protein-base contracts) and "indirect readout" (protein-phosphate contacts and DNA conformation) of the DNA sequence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lesser, D R -- Kurpiewski, M R -- Jen-Jacobson, L -- GM-29207/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 9;250(4982):776-86.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of Pittsburgh, PA 15260.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2237428" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; DNA/chemistry/genetics/*metabolism ; Deoxyribonuclease EcoRI/chemistry/*metabolism ; Energy Transfer ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phosphates/metabolism ; Substrate Specificity
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  • 74
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-17
    Description: A class of transcriptional regulator proteins bind to DNA at dyad-symmetric sites through a motif consisting of (i) a "leucine zipper" sequence that associates into noncovalent, parallel, alpha-helical dimers and (ii) a covalently connected basic region necessary for binding DNA. The basic regions are predicted to be disordered in the absence of DNA and to form alpha helices when bound to DNA. These helices bind in the major groove forming multiple hydrogen-bonded and van der Waals contacts with the nucleotide bases. To test this model, two peptides were designed that were identical to natural leucine zipper proteins only at positions hypothesized to be critical for dimerization and DNA recognition. The peptides form dimers that bind specifically to DNA with their basic regions in alpha-helical conformations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Neil, K T -- Hoess, R H -- DeGrado, W F -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):774-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Central Research and Development Department, E.I. du Pont de Nemours & Co., Wilmington, DE 19880-0328.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2389143" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Chemistry, Physical ; Circular Dichroism ; Computer Simulation ; DNA/*metabolism ; DNA-Binding Proteins/*metabolism ; Hydrogen Bonding ; *Leucine ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Physicochemical Phenomena ; Protein Conformation
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  • 75
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-10-26
    Description: Expression of the L-arabinose BAD operon in Escherichia coli is regulated by AraC protein which acts both positively in the presence of arabinose to induce transcription and negatively in the absence of arabinose to repress transcription. The repression of the araBAD promoter is mediated by DNA looping between AraC protein bound at two sites near the promoter separated by 210 base pairs, araI and araO2. In vivo and in vitro experiments presented here show that an AraC dimer, with binding to half of araI and to araO2, maintains the repressed state of the operon. The addition of arabinose, which induces the operon, breaks the loop, and shifts the interactions from the distal araO2 site to the previously unoccupied half of the araI site. The conversion between the two states does not require additional binding of AraC protein and appears to be driven largely by properties of the protein rather than being specified by the slightly different DNA sequences of the binding sites. Slight reorientation of the subunits of AraC could specify looping or unlooping by the protein. Such a mechanism could account for regulation of DNA looping in other systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lobell, R B -- Schleif, R F -- GM18277/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Oct 26;250(4980):528-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Department of Biochemistry, Brandeis University, Waltham, MA 02254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2237403" target="_blank"〉PubMed〈/a〉
    Keywords: AraC Transcription Factor ; Arabinose/genetics/pharmacology ; *Bacterial Proteins ; Binding Sites ; *DNA, Bacterial/genetics/metabolism ; DNA, Superhelical/metabolism ; Escherichia coli/*genetics ; Escherichia coli Proteins ; Fucose/pharmacology ; Gene Expression Regulation, Bacterial/*drug effects ; Guanine/metabolism ; Macromolecular Substances ; Methylation ; Mutation ; Nucleic Acid Conformation/*drug effects ; Operon ; Protein Conformation/drug effects ; Repressor Proteins/metabolism/*pharmacology ; *Transcription Factors
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  • 76
    Publication Date: 1990-09-21
    Description: Thyrotropin (TSH), luteinizing hormone (LH), and chorionic gonadotropin (CG) are structurally related glycoprotein hormones, which bind to receptors that share a high degree of sequence similarity. However, comparison of the primary amino acid sequences of the TSH and LH-CG receptors reveals two unique insertions of 8 and 50 amino acids in the extracellular domain of the TSH receptor. The functional significance of these insertions were determined by site-directed mutagenesis. Deletion of the 50-amino acid tract (residues 317 to 366) had no effect on TSH binding or on TSH and thyroid-stimulating immunoglobulin (TSI) biological activities. In contrast, either deletion or substitution of the eight-amino acid region (residues 38 to 45) abolished these activities. This eight-amino acid tract near the amino terminus of the TSH receptor appears to be an important site of interaction for both TSH and TSI.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadsworth, H L -- Chazenbalk, G D -- Nagayama, Y -- Russo, D -- Rapoport, B -- DK-19289/DK/NIDDK NIH HHS/ -- DK-36182/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 21;249(4975):1423-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Veterans Administration Medical Center, San Francisco, CA 94121.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2169649" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Cell Line ; Chromosome Deletion ; Clone Cells ; Cyclic AMP/metabolism ; Humans ; Molecular Sequence Data ; Mutation ; Oligonucleotide Probes ; Receptors, Thyrotropin/*genetics/metabolism ; Thyrotropin/*metabolism/pharmacology ; Transfection
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  • 77
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-10-26
    Description: The yeast protein RAP1, initially described as a transcriptional regulator, binds in vitro to sequences found in a number of seemingly unrelated genomic loci. These include the silencers at the transcriptionally repressed mating-type genes, the promoters of many genes important for cell growth, and the poly[(cytosine)1-3 adenine] [poly(C1-3A)] repeats of telomeres. Because RAP1 binds in vitro to the poly(C1-3A) repeats of telomeres, it has been suggested that RAP1 may be involved in telomere function in vivo. In order to test this hypothesis, the telomere tract lengths of yeast strains that contained conditionally lethal (ts) rap1 mutations were analyzed. Several rap1ts alleles reduced telomere length in a temperature-dependent manner. In addition, plasmids that contain small, synthetic telomeres with intact or mutant RAP1 binding sites were tested for their ability to function as substrates for poly(C1-3A) addition in vivo. Mutations in the RAP1 binding sites reduced the efficiency of the addition reaction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lustig, A J -- Kurtz, S -- Shore, D -- GM 40094/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Oct 26;250(4980):549-53.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2237406" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Chromosomes, Fungal/metabolism/*ultrastructure ; DNA-Binding Proteins/metabolism ; Fungal Proteins/genetics/*metabolism ; *Genes, Fungal ; *Genes, Mating Type, Fungal ; Molecular Sequence Data ; Mutation ; Plasmids ; Poly A/metabolism ; Poly C/metabolism ; Repetitive Sequences, Nucleic Acid ; Saccharomyces cerevisiae/*genetics ; Temperature ; *Transcription Factors ; Transformation, Genetic
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  • 78
    Publication Date: 1990-07-27
    Description: The enzymatic degradation of cellulose is an important process, both ecologically and commercially. The three-dimensional structure of a cellulase, the enzymatic core of CBHII from the fungus Trichoderma reesei reveals an alpha-beta protein with a fold similar to but different from the widely occurring barrel topology first observed in triose phosphate isomerase. The active site of CBHII is located at the carboxyl-terminal end of a parallel beta barrel, in an enclosed tunnel through which the cellulose threads. Two aspartic acid residues, located in the center of the tunnel are the probable catalytic residues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rouvinen, J -- Bergfors, T -- Teeri, T -- Knowles, J K -- Jones, T A -- New York, N.Y. -- Science. 1990 Jul 27;249(4967):380-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, BMC, Uppsala, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2377893" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Cellulose/metabolism ; Cellulose 1,4-beta-Cellobiosidase ; Chemistry, Physical ; Crystallization ; Crystallography ; *Glycoside Hydrolases/metabolism ; Glycosylation ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Mitosporic Fungi/*enzymology ; Molecular Sequence Data ; Molecular Structure ; Physicochemical Phenomena ; Protein Conformation ; Trichoderma/*enzymology
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  • 79
    Publication Date: 1990-08-31
    Description: The isocitrate dehydrogenase of Escherichia coli is an example of a ubiquitous class of enzymes that are regulated by covalent modification. In the three-dimensional structure of the enzyme-substrate complex, isocitrate forms a hydrogen bond with Ser113, the site of regulatory phosphorylation. The structures of Asp113 and Glu113 mutants, which mimic the inactivation of the enzyme by phosphorylation, show minimal conformational changes from wild type, as in the phosphorylated enzyme. Calculations based on observed structures suggest that the change in electrostatic potential when a negative charge is introduced either by phosporylation or site-directed mutagenesis is sufficient to inactivate the enzyme. Thus, direct interaction at a ligand binding site is an alternative mechanism to induced conformational changes from an allosteric site in the regulation of protein activity by phosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hurley, J H -- Dean, A M -- Sohl, J L -- Koshland, D E Jr -- Stroud, R M -- GM 24485/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 31;249(4972):1012-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2204109" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Escherichia coli/*enzymology/genetics ; Homeostasis ; Isocitrate Dehydrogenase/genetics/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Phosphorylation ; Protein Conformation
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  • 80
    Publication Date: 1990-03-09
    Description: Comparison of a lambda repressor-operator complex and a 434 repressor-operator complex reveals that three conserved residues in the helix-turn-helix (HTH) region make similar contacts in each of the crystallographically determined structures. These conserved residues and their interactions with phosphodiester oxygens help establish a frame of reference within which other HTH residues make contacts that are critical for site-specific recognition. Such "positioning contacts" may be important conserved features within families of HTH proteins. In contrast, the structural comparisons appear to rule out any simple "recognition code" at the level of detailed side chain-base pair interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pabo, C O -- Aggarwal, A K -- Jordan, S R -- Beamer, L J -- Obeysekare, U R -- Harrison, S C -- GM 29109/GM/NIGMS NIH HHS/ -- GM 31471/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Mar 9;247(4947):1210-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2315694" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Asparagine ; Base Composition ; Base Sequence ; Binding Sites ; *DNA-Binding Proteins ; Glutamine ; Hydrogen Bonding ; Molecular Sequence Data ; Molecular Structure ; *Operator Regions, Genetic ; Protein Conformation ; Repressor Proteins/*metabolism ; Transcription Factors/*metabolism ; Viral Proteins ; Viral Regulatory and Accessory Proteins
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  • 81
    Publication Date: 1990-04-06
    Description: A complementary DNA (cDNA) clone that encodes inositol 1,4,5-trisphosphate 3-kinase was isolated from a rat brain cDNA expression library with the use of monoclonal antibodies. This clone had an open reading frame that would direct the synthesis of a protein consisting of 449 amino acids and with a molecular mass of 49,853 daltons. The putative protein revealed a potential calmodulin-binding site and six regions with amino acid compositions (PEST regions) common to proteins that are susceptible to calpain. Expression of the cDNA in COS cells resulted in an approximately 150-fold increase in inositol 1,4,5-trisphosphate 3-kinase activity of these cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, K Y -- Kim, H K -- Lee, S Y -- Moon, K H -- Sim, S S -- Kim, J W -- Chung, H K -- Rhee, S G -- New York, N.Y. -- Science. 1990 Apr 6;248(4951):64-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2157285" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Brain/enzymology ; Calcium/metabolism ; Calmodulin/metabolism ; Calpain/antagonists & inhibitors/pharmacology ; Cell Line ; *Cloning, Molecular ; Codon ; DNA/*genetics ; *Gene Expression ; Molecular Sequence Data ; Molecular Weight ; Phosphotransferases/*genetics/metabolism ; *Phosphotransferases (Alcohol Group Acceptor) ; Plasmids ; Rats ; Transfection
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  • 82
    Publication Date: 1990-07-20
    Description: The crystallographic structure of a recombinant hirudin-thrombin complex has been solved at 2.3 angstrom (A) resolution. Hirudin consists of an NH2-terminal globular domain and a long (39 A) COOH-terminal extended domain. Residues Ile1 to Tyr3 of hirudin form a parallel beta-strand with Ser214 to Glu217 of thrombin with the nitrogen atom of Ile1 making a hydrogen bond with Ser195 O gamma atom of the catalytic site, but the specificity pocket of thrombin is not involved in the interaction. The COOH-terminal segment makes numerous electrostatic interactions with an anion-binding exosite of thrombin, whereas the last five residues are in a helical loop that forms many hydrophobic contacts. In all, 27 of the 65 residues of hirudin have contacts less than 4.0 A with thrombin (10 ion pairs and 23 hydrogen bonds). Such abundant interactions may account for the high affinity and specificity of hirudin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rydel, T J -- Ravichandran, K G -- Tulinsky, A -- Bode, W -- Huber, R -- Roitsch, C -- Fenton, J W 2nd -- HL13160/HL/NHLBI NIH HHS/ -- HL43229/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Jul 20;249(4966):277-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Michigan State University, East Lansing 48824.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2374926" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Hirudins/*metabolism ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Conformation ; Recombinant Proteins/metabolism ; Thrombin/*metabolism ; X-Ray Diffraction
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  • 83
    Publication Date: 1990-05-25
    Description: An active site, cofactor-containing peptide has been obtained in high yield from bovine serum amine oxidase. Sequencing of this pentapeptide indicates: Leu-Asn-X-Asp-Tyr. Analysis of the peptide by mass spectrometry, ultraviolet-visible spectroscopy, and proton nuclear magnetic resonance leads to the identification of X as 6-hydroxydopa. This result indicates that, contrary to previous proposals, pyrroloquinoline quinone is not the active site cofactor in mammalian copper amine oxidases. Although 6-hydroxydopa has been implicated in neurotoxicity, the data presented suggest that this compound has a functional role at an enzyme active site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janes, S M -- Mu, D -- Wemmer, D -- Smith, A J -- Kaur, S -- Maltby, D -- Burlingame, A L -- Klinman, J P -- GM 39296/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 May 25;248(4958):981-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2111581" target="_blank"〉PubMed〈/a〉
    Keywords: *Amine Oxidase (Copper-Containing) ; Amino Acid Sequence ; Animals ; Binding Sites ; Cattle ; Copper ; Dihydroxyphenylalanine/*analogs & derivatives/metabolism ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Molecular Sequence Data ; Oxidoreductases/metabolism ; Oxidoreductases Acting on CH-NH Group Donors/blood/*metabolism ; Peptide Fragments/analysis/chemical synthesis ; Quinones/metabolism ; Spectrophotometry, Ultraviolet
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  • 84
    Publication Date: 1990-12-21
    Description: Human growth hormone (hGH) elicits a diverse set of biological activities including lactation that derives from binding to the prolactin (PRL) receptor. The binding affinity of hGH for the extracellular binding domain of the hPRL receptor (hPRLbp) was increased about 8000-fold by addition of 50 micromolar ZnCl2. Zinc was not required for binding of hGH to the hGH binding protein (hGHbp) or for binding of hPRL to the hPRLbp. Other divalent metal ions (Ca2+, Mg2+, Cu2+, Mn2+, and Co2+) at physiological concentrations did not support such strong binding. Scatchard analysis indicated a stoichiometry of one Zn2+ per hGH.hPRLbp complex. Mutational analysis showed that a cluster of three residues (His18, His21, and Glu174) in hGH and His188 from the hPRLbp (conserved in all PRL receptors but not GH receptors) are probable Zn2+ ligands. This polypeptide hormone.receptor "zinc sandwich" provides a molecular mechanism to explain why nonprimate GHs are not lactogenic and offers a molecular link between zinc deficiency and its association with altered functions of hGH.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cunningham, B C -- Bass, S -- Fuh, G -- Wells, J A -- New York, N.Y. -- Science. 1990 Dec 21;250(4988):1709-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2270485" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Chlorides/*pharmacology ; Growth Hormone/*metabolism ; Humans ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligonucleotide Probes ; Plasmids ; Protein Conformation ; Receptors, Prolactin/drug effects/genetics/*metabolism ; Restriction Mapping ; Zinc/metabolism/*pharmacology ; *Zinc Compounds
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  • 85
    Publication Date: 1990-12-21
    Description: The mechanism by which transcription factors stimulate DNA replication in eukaryotes is unknown. Bovine papillomavirus DNA synthesis requires the products of the viral E1 gene and the transcriptional activator protein encoded by the E2 gene. Experimental data showed that the 68-kilodalton (kD) E1 protein formed a complex with the 48-kD E2 transcription factor. This complex bound specifically to the viral origin of replication, which contains multiple binding sites for E2. Repressor proteins encoded by the E2 open reading frame failed to complex with E1 suggesting that the 162-amino acid region of E2 that participates in transactivation contained critical determinants for interaction with E1. The physical association between a replication protein and a transcription factor suggests that transcriptional activator proteins may function in targeting replication initiator proteins to their respective origins of replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohr, I J -- Clark, R -- Sun, S -- Androphy, E J -- MacPherson, P -- Botchan, M R -- CA-30490/CA/NCI NIH HHS/ -- CA-42414/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 21;250(4988):1694-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkely 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2176744" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Bovine papillomavirus 1/*genetics ; Cell Line ; *DNA Replication ; DNA, Viral/biosynthesis/genetics ; DNA-Binding Proteins/*metabolism ; Genes, Viral ; Open Reading Frames ; Protein Binding ; Repressor Proteins/*metabolism ; Transcription Factors/*metabolism ; Viral Proteins/*metabolism
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  • 86
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-17
    Description: A recently described class of DNA binding proteins is characterized by the "bZIP" motif, which consists of a basic region that contacts DNA and an adjacent "leucine zipper" that mediates protein dimerization. A peptide model for the basic region of the yeast transcriptional activator GCN4 has been developed in which the leucine zipper has been replaced by a disulfide bond. The 34-residue peptide dimer, but not the reduced monomer, binds DNA with nanomolar affinity at 4 degrees C. DNA binding is sequence-specific as judged by deoxyribonuclease I footprinting. Circular dichroism spectroscopy suggests that the peptide adopts a helical structure when bound to DNA. These results demonstrate directly that the GCN4 basic region is sufficient for sequence-specific DNA binding and suggest that a major function of the GCN4 leucine zipper is simply to mediate protein dimerization. Our approach provides a strategy for the design of short sequence-specific DNA binding peptides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Talanian, R V -- McKnight, C J -- Kim, P S -- GM13665/GM/NIGMS NIH HHS/ -- GM44162/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):769-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Nine Cambridge Center, MA 02142.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2389142" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Circular Dichroism ; DNA/*metabolism ; DNA-Binding Proteins/*metabolism ; Deoxyribonuclease I ; Disulfides ; Fungal Proteins/*metabolism ; Leucine ; Macromolecular Substances ; Molecular Sequence Data ; Peptides/*metabolism ; Protein Conformation ; *Protein Kinases ; *Saccharomyces cerevisiae Proteins ; Transcription Factors/*metabolism
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  • 87
    Publication Date: 1990-02-23
    Description: Bacterial MerR proteins are dimeric DNA-binding proteins that mediate the Hg(II)-dependent induction of mercury resistance operons. Site-directed mutagenesis of the Bacillus sp. RC607 MerR protein reveals that three of four Cys residues per monomer are required for Hg(II) binding at the single high-affinity binding site. Inactive mutant homodimers can exchange subunits to form heterodimers active for Hg(II) binding. Studies of a heterodimer retaining only three of eight cysteine residues per dimer reveal that Cys79 in one subunit and Cys114 and Cys123 in the second subunit are necessary and sufficient for high-affinity Hg(II) binding in an asymmetric, subunit bridging coordination complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmann, J D -- Ballard, B T -- Walsh, C T -- GM20011/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Feb 23;247(4945):946-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2305262" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacillus/*analysis/genetics ; Bacterial Proteins/genetics/*metabolism ; Base Sequence ; Binding Sites ; Cations ; DNA-Binding Proteins/genetics/*metabolism ; Macromolecular Substances ; Mercury/*metabolism ; Molecular Sequence Data ; Mutation ; Structure-Activity Relationship
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  • 88
    Publication Date: 1990-11-23
    Description: The CD4 antigen is the high affinity cellular receptor for the human immunodeficiency virus type-1 (HIV-1). Binding of recombinant soluble CD4 (sCD4) or the purified V1 domain of sCD4 to the surface glycoprotein gp120 on virions resulted in rapid dissociation of gp120 from its complex with the transmembrane glycoprotein gp41. This may represent the initial stage in virus-cell and cell-cell fusion. Shedding of gp120 from virions induced by sCD4 may also contribute to the mechanism by which these soluble receptor molecules neutralize HIV-1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, J P -- McKeating, J A -- Weiss, R A -- Sattentau, Q J -- New York, N.Y. -- Science. 1990 Nov 23;250(4984):1139-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2251501" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/pharmacology ; Antigens, CD4/immunology/*metabolism ; Binding Sites ; Binding, Competitive ; Cell Line ; Cricetinae ; HIV Envelope Protein gp120/*metabolism ; HIV Envelope Protein gp41/metabolism ; HIV-1/*metabolism ; Virion/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 89
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roberts, L -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):744.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2117777" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; GTPase-Activating Proteins ; Genes, ras ; Humans ; Neurofibromatosis 1/*genetics ; Proteins/genetics ; Sequence Homology, Nucleic Acid ; ras GTPase-Activating Proteins
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  • 90
    Publication Date: 1990-01-05
    Description: Receptor binding studies show that resistance of a laboratory-selected Plodia interpunctella strain to a Bacillus thuringiensis insecticidal crystal protein (ICP) is correlated with a 50-fold reduction in affinity of the membrane receptor for this protein. The strain is sensitive to a second type of ICP that apparently recognizes a different receptor. Understanding the mechanism of resistance will provide strategies to prevent or delay resistance and hence prolong the usefulness of B. thuringiensis ICPs as environmentally safe insecticides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Rie, J -- McGaughey, W H -- Johnson, D E -- Barnett, B D -- Van Mellaert, H -- New York, N.Y. -- Science. 1990 Jan 5;247(4938):72-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Genetic Systems, Gent, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2294593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bacillus thuringiensis ; *Bacterial Proteins/metabolism ; Bacterial Toxins/metabolism ; Binding Sites ; Cell Membrane/metabolism ; *Endotoxins ; Hemolysin Proteins ; Insecticide Resistance/*physiology ; *Lepidoptera ; Microvilli/metabolism ; *Moths ; *Pest Control, Biological ; Receptors, Drug/metabolism
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  • 91
    Publication Date: 1990-12-14
    Description: A chemical description of the action of phospholipase A2 (PLA2) can now be inferred with confidence from three high-resolution x-ray crystal structures. The first is the structure of the PLA2 from the venom of the Chinese cobra (Naja naja atra) in a complex with a phosphonate transition-state analogue. This enzyme is typical of a large, well-studied homologous family of PLA2S. The second is a similar complex with the evolutionarily distant bee-venom PLA2. The third structure is the uninhibited PLA2 from Chinese cobra venom. Despite the different molecular architectures of the cobra and bee-venom PLA2s, the transition-state analogue interacts in a nearly identical way with the catalytic machinery of both enzymes. The disposition of the fatty-acid side chains suggests a common access route of the substrate from its position in the lipid aggregate to its productive interaction with the active site. Comparison of the cobra-venom complex with the uninhibited enzyme indicates that optimal binding and catalysis at the lipid-water interface is due to facilitated substrate diffusion from the interfacial binding surface to the catalytic site rather than an allosteric change in the enzyme's structure. However, a second bound calcium ion changes its position upon the binding of the transition-state analogue, suggesting a mechanism for augmenting the critical electrophile.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443688/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443688/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scott, D L -- White, S P -- Otwinowski, Z -- Yuan, W -- Gelb, M H -- Sigler, P B -- GM22324/GM/NIGMS NIH HHS/ -- HL36235/HL/NHLBI NIH HHS/ -- R01 HL036235/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 14;250(4987):1541-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2274785" target="_blank"〉PubMed〈/a〉
    Keywords: Bee Venoms/analysis ; Binding Sites ; Calcium/metabolism ; Catalysis ; Chemistry, Physical ; Cobra Venoms/analysis ; Models, Molecular ; Molecular Structure ; Organophosphonates/metabolism ; Phospholipases A/chemistry/*metabolism ; Phospholipases A2 ; Phospholipids/metabolism ; Physicochemical Phenomena ; Protein Conformation ; X-Ray Diffraction
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  • 92
    Publication Date: 1990-12-14
    Description: The 2.0 angstroms crystal structure of a complex containing bee-venom phospholipase A2 (PLA2) and a phosphonate transition-state analogue was solved by multiple isomorphous replacement. The electron-density map is sufficiently detailed to visualize the proximal sugars of the enzyme's N-linked carbohydrate and a single molecule of the transition-state analogue bound ot its active center. Although bee-venom PLA2 does not belong to the large homologous Class I/II family that encompasses most other well-studied PLA2s, there is segmental sequence similarity and conservation of many functional substructures. Comparison of the bee-venom enzyme with other phospholipase structures provides compelling evidence for a common catalytic mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scott, D L -- Otwinowski, Z -- Gelb, M H -- Sigler, P B -- GM22324/GM/NIGMS NIH HHS/ -- HL36235/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 14;250(4987):1563-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2274788" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bee Venoms/*analysis ; Binding Sites ; Calcium/metabolism ; Carbohydrate Metabolism ; Catalysis ; Chemistry, Physical ; Crystallization ; Hydrogen Bonding ; Molecular Sequence Data ; Molecular Structure ; Phosphatidylethanolamines/*metabolism ; Phospholipases A/*chemistry/metabolism ; Phospholipases A2 ; Physicochemical Phenomena ; Protein Conformation
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  • 93
    Publication Date: 1990-03-09
    Description: The T cell antigen receptor (TCR) delta gene is located within the TCR alpha locus. A T cell-specific transcriptional enhancer, distinct from the TCR alpha enhancer, has been identified within the J delta 3-C delta intron of the human T cell receptor delta gene. This enhancer activates transcription from the V delta 1 and V delta 3 promoters as well as from heterologous promoters. Enhancer activity has been localized to a 250-bp region that contains multiple binding sites for nuclear proteins. Thus, transcriptional control of the TCR delta and TCR alpha genes is mediated by distinct regulatory elements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Redondo, J M -- Hata, S -- Brocklehurst, C -- Krangel, M S -- R01-GM41052/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Mar 9;247(4947):1225-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2156339" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Cell Line ; Chloramphenicol O-Acetyltransferase/genetics ; DNA Restriction Enzymes ; Deoxyribonuclease I ; Enhancer Elements, Genetic/*genetics ; Gene Rearrangement ; Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor ; Humans ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/metabolism ; Plasmids ; Promoter Regions, Genetic/genetics ; Receptors, Antigen, T-Cell/*genetics ; Repetitive Sequences, Nucleic Acid ; *Transcription, Genetic ; Transfection
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  • 94
    Publication Date: 1990-06-25
    Description: Lipoprotein-associated coagulation inhibitor (LACI) appears to inhibit tissue factor (TF)-induced blood coagulation by forming a quaternary inhibitory complex containing factor Xa, LACI, factor VIIa, and TF. A genetically engineered hybrid protein consisting of the light chain of factor Xa and the first Kunitz-type inhibitor domain of LACI is shown to directly inhibit the activity of the factor VIIa-TF catalytic complex. Unlike inhibition of factor VIIa-TF activity by native LACI, inhibition by the hybrid protein is not dependent on factor Xa. In an assay of TF-induced coagulation, 50% TF inhibition occurs with hybrid protein at 35 nanograms per milliliter, whereas LACI at 2.5 micrograms per milliliter is required for an equivalent effect. gamma-Carboxylation of glutamic acid residues in the factor Xa light chain portion of the hybrid protein is required for inhibitory activity, indicating that the first Kunitz-type domain of LACI alone is not sufficient for inhibition of factor VIIa-TF.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Girard, T J -- MacPhail, L A -- Likert, K M -- Novotny, W F -- Miletich, J P -- Broze, G J Jr -- New York, N.Y. -- Science. 1990 Jun 15;248(4961):1421-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology/Oncology, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1972598" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Carboxyglutamic Acid/metabolism ; Amino Acid Sequence ; Animals ; Binding Sites ; Calcium/metabolism ; Cell Line ; Cloning, Molecular ; Factor VII/antagonists & inhibitors/metabolism/*pharmacology ; Factor VIIa/*antagonists & inhibitors/metabolism ; Factor Xa/metabolism/*pharmacology ; Fibroblasts/metabolism ; Glutamates/metabolism ; Glutamic Acid ; Lipoproteins/metabolism/*pharmacology ; Mice ; Molecular Sequence Data ; Papillomaviridae ; Protease Inhibitors/*pharmacology ; Protein Sorting Signals ; Recombinant Fusion Proteins/*pharmacology ; Thromboplastin/antagonists & inhibitors/metabolism/*pharmacology ; Transfection
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  • 95
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-05-25
    Description: The viral protein p6, required for the protein-primed initiation of replication of Bacillus subtilis phage phi 29, forms a nucleoprotein complex at the viral replication origins that shows novel features. Deoxyribonuclease I and hydroxyl radical footprinting data, as well as the induction of positive supercoiling, support a model in which a DNA right-handed superhelix tightly wraps around a multimeric p6 core. The interaction occurs through the DNA minor groove. The activity of p6 not only requires the formation of the complex but also its correct positioning, indicating that the other proteins involved in the initiation of replication recognize, at a precise position, either the p6 core or the DNA conformational change induced by p6.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Serrano, M -- Salas, M -- Hermoso, J M -- 5 R01 GM 27242-10/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 May 25;248(4958):1012-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centro de Biologia Molecular (CSIC-UAM), Universidad Autonoma, Madrid, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2111580" target="_blank"〉PubMed〈/a〉
    Keywords: Bacillus subtilis ; Bacteriophages/*genetics ; Base Sequence ; Binding Sites ; *DNA Replication ; DNA, Superhelical/metabolism ; DNA-Binding Proteins/*ultrastructure ; Deoxyribonucleoproteins/*metabolism/ultrastructure ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligonucleotides ; Viral Proteins/metabolism/ultrastructure ; Virus Replication
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  • 96
    Publication Date: 1990-12-14
    Description: The crystal structure of a complex between a phosphonate transition-state analogue and the phospholipase A2 (PLA2) from Naja naja atra venom has been solved and refined to a resolution of 2.0 angstroms. The identical stereochemistry of the two complexes that comprise the crystal's asymmetric unit indicates both the manner in which the transition state is stabilized and how the hydrophobic fatty acyl chains of the substrate are accommodated by the enzyme during interfacial catalysis. The critical features that suggest the chemistry of binding and catalysis are the same as those seen in the crystal structure of a similar complex formed with the evolutionarily distant bee-venom PLA2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉White, S P -- Scott, D L -- Otwinowski, Z -- Gelb, M H -- Sigler, P B -- GM22324/GM/NIGMS NIH HHS/ -- HL 36235/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 14;250(4987):1560-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2274787" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bee Venoms/analysis ; Binding Sites ; Calcium/metabolism ; Catalysis ; Chemistry, Physical ; Cobra Venoms/*analysis ; Crystallization ; Hydrogen Bonding ; Molecular Sequence Data ; Molecular Structure ; Phosphatidylethanolamines/*metabolism ; Phospholipases A/*chemistry/metabolism ; Phospholipases A2 ; Physicochemical Phenomena ; Protein Conformation
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  • 97
    Publication Date: 1990-07-20
    Description: The 70-residue carboxyl-terminal domain of the muscle contractile protein troponin-C contains two helix-loop-helix calcium (Ca)-binding sites that are related to each other by approximate twofold rotational symmetry. Hydrophobic residues from the helices and a short three residue beta sheet at the interface of the two sites act to stabilize the protein domain in the presence of Ca. A synthetic 34-residue peptide representing one of these sites (site III) has been synthesized and studied by H-1 nuclear magnetic resonance (NMR) spectroscopy. In solution this peptide undergoes a Ca-induced conformational change to form the helix-loop-helix Ca-binding motif. Two-dimensional nuclear Overhauser effect spectra have provided evidence for the formation of a beta sheet and interactions between several hydrophobic residues from opposing helices as found in troponin-C. It is proposed that a symmetric two-site dimer similar in tertiary structure to the carboxyl-terminal domain of troponin-C forms from the assembly of two site III peptides in the Ca-bound form.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaw, G S -- Hodges, R S -- Sykes, B D -- New York, N.Y. -- Science. 1990 Jul 20;249(4966):280-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Alberta, Edmonton, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2374927" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Calcium/*metabolism/pharmacology ; Hydrogen ; Magnetic Resonance Spectroscopy/methods ; Models, Molecular ; Molecular Sequence Data ; Peptides/chemical synthesis/*metabolism ; Protein Conformation ; Troponin/chemical synthesis/*metabolism ; Troponin C ; Turkeys
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  • 98
    Publication Date: 1990-04-27
    Description: The gene encoding the 49-kilodalton protein that undergoes light-induced phosphorylation in the Drosophila photoreceptor has been isolated and characterized. The encoded protein has 401 amino acid residues and a molecular mass of 44,972 daltons, and it shares approximately 42 percent amino acid sequence identity with arrestin (S-antigen), which has been proposed to quench the light-induced cascade of guanosine 3',5'-monophosphate hydrolysis in vertebrate photoreceptors. Unlike the 49-kilodalton protein, however, arrestin, which appears to bind to phosphorylated rhodopsin, has not itself been reported to undergo phosphorylation. In vitro, Ca2+ was the only agent found that would stimulate the phosphorylation of the 49-kilodalton protein. The phosphorylation of this arrestin-like protein in vivo may therefore be triggered by a Ca2+ signal that is likely to be regulated by light-activated phosphoinositide-specific phospholipase C.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamada, T -- Takeuchi, Y -- Komori, N -- Kobayashi, H -- Sakai, Y -- Hotta, Y -- Matsumoto, H -- EY06595/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1990 Apr 27;248(4954):483-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2158671" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Antigens ; Arrestin ; Binding Sites ; Calcium/pharmacology ; Cloning, Molecular ; Cyclic GMP/metabolism ; DNA/genetics ; Drosophila melanogaster/*genetics ; Enzyme Activation/drug effects ; *Eye Proteins ; Isoelectric Point ; Molecular Sequence Data ; Molecular Weight ; Mutation ; Phosphatidylinositol Diacylglycerol-Lyase ; *Phosphoproteins/genetics/metabolism ; Phosphoric Diester Hydrolases/metabolism ; Phosphorylation ; Photoreceptor Cells/*analysis ; Protein Biosynthesis ; Restriction Mapping ; Sequence Homology, Nucleic Acid
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  • 99
    Publication Date: 1990-02-23
    Description: Ras proteins participate as a molecular switch in the early steps of the signal transduction pathway that is associated with cell growth and differentiation. When the protein is in its GTP complexed form it is active in signal transduction, whereas it is inactive in its GDP complexed form. A comparison of eight three-dimensional structures of ras proteins in four different crystal lattices, five with a nonhydrolyzable GTP analog and three with GDP, reveals that the "on" and "off" states of the switch are distinguished by conformational differences that span a length of more than 40 A, and are induced by the gamma-phosphate. The most significant differences are localized in two regions: residues 30 to 38 (the switch I region) in the second loop and residues 60 to 76 (the switch II region) consisting of the fourth loop and the short alpha-helix that follows the loop. Both regions are highly exposed and form a continuous strip on the molecular surface most likely to be the recognition sites for the effector and receptor molecule(or molecules). The conformational differences also provide a structural basis for understanding the biological and biochemical changes of the proteins due to oncogenic mutations, autophosphorylation, and GTP hydrolysis, and for understanding the interactions with other proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Milburn, M V -- Tong, L -- deVos, A M -- Brunger, A -- Yamaizumi, Z -- Nishimura, S -- Kim, S H -- CA45593/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Feb 23;247(4945):939-45.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2406906" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallization ; Crystallography ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; Humans ; Models, Molecular ; Molecular Structure ; Protein Conformation ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins p21(ras) ; *Signal Transduction ; Structure-Activity Relationship
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 1990-09-21
    Description: Ribonuclease H digests the RNA strand of duplex RNA.DNA hybrids into oligonucleotides. This activity is indispensable for retroviral infection and is involved in bacterial replication. The ribonuclease H from Escherichia coli is homologous with the retroviral proteins. The crystal structure of the E. coli enzyme reveals a distinctive alpha-beta tertiary fold. Analysis of the molecular model implicates a carboxyl triad in the catalytic mechanism and suggests a likely mode for the binding of RNA.DNA substrates. The structure was determined by the method of multiwavelength anomalous diffraction (MAD) with the use of synchrotron data from a crystal of the recombinant selenomethionyl protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, W -- Hendrickson, W A -- Crouch, R J -- Satow, Y -- GM 34102/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 21;249(4975):1398-405.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2169648" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Computer Graphics ; *Endoribonucleases/genetics ; Escherichia coli/enzymology ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Recombinant Proteins ; Ribonuclease H ; *Selenium ; *Selenomethionine ; Sequence Homology, Nucleic Acid ; X-Ray Diffraction/methods
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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