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  • Cell Line  (142)
  • Binding Sites  (116)
  • American Association for the Advancement of Science (AAAS)  (250)
  • American Institute of Physics (AIP)
  • Oxford University Press
  • 2010-2014
  • 1995-1999  (141)
  • 1990-1994  (109)
  • 1995  (141)
  • 1991  (109)
Collection
Publisher
  • American Association for the Advancement of Science (AAAS)  (250)
  • American Institute of Physics (AIP)
  • Oxford University Press
Years
  • 2010-2014
  • 1995-1999  (141)
  • 1990-1994  (109)
Year
  • 1
    Publication Date: 1995-04-28
    Description: DCoH, the dimerization cofactor of hepatocyte nuclear factor-1, stimulates gene expression by associating with specific DNA binding proteins and also catalyzes the dehydration of the biopterin cofactor of phenylalanine hydroxylase. The x-ray crystal structure determined at 3 angstrom resolution reveals that DCoH forms a tetramer containing two saddle-shaped grooves that comprise likely macromolecule binding sites. Two equivalent enzyme active sites flank each saddle, suggesting that there is a spatial connection between the catalytic and binding activities. Structural similarities between the DCoH fold and nucleic acid-binding proteins argue that the saddle motif has evolved to bind diverse ligands or that DCoH unexpectedly may bind nucleic acids.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Endrizzi, J A -- Cronk, J D -- Wang, W -- Crabtree, G R -- Alber, T -- New York, N.Y. -- Science. 1995 Apr 28;268(5210):556-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley 94720-3206, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7725101" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Computer Graphics ; Crystallography, X-Ray ; Gene Expression Regulation ; Hydro-Lyases/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; Transcription Factors/*chemistry/metabolism
    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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  • 2
    Publication Date: 1995-07-14
    Description: CD1 molecules are distantly related to the major histocompatibility complex (MHC) class I proteins. They are of unknown function. Screening random peptide phage display libraries with soluble empty mouse CD1 (mCD1) identified a peptide binding motif. It consists of three anchor positions occupied by aromatic or bulky hydrophobic amino acids. Equilibrium binding studies demonstrated that mCD1 binds peptides containing the appropriate motif with relatively high affinity. However, in contrast to classical MHC class I molecules, strong binding to mCD1 required relatively long peptides. Peptide-specific, mCD1-restricted T cell responses can be raised, which suggests that the findings are of immunological significance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Castano, A R -- Tangri, S -- Miller, J E -- Holcombe, H R -- Jackson, M R -- Huse, W D -- Kronenberg, M -- Peterson, P A -- New York, N.Y. -- Science. 1995 Jul 14;269(5221):223-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7542403" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Antigen Presentation ; Antigens, CD/chemistry/*immunology/metabolism ; Antigens, CD1 ; Cell Line ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Peptides/chemistry/*immunology/metabolism ; T-Lymphocytes, Cytotoxic/*immunology ; Transfection
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 1995-09-01
    Description: Eukaryotic chromosomes are capped with repetitive telomere sequences that protect the ends from damage and rearrangements. Telomere repeats are synthesized by telomerase, a ribonucleic acid (RNA)-protein complex. Here, the cloning of the RNA component of human telomerase, termed hTR, is described. The template region of hTR encompasses 11 nucleotides (5'-CUAACCCUAAC) complementary to the human telomere sequence (TTAGGG)n. Germline tissues and tumor cell lines expressed more hTR than normal somatic cells and tissues, which have no detectable telomerase activity. Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity. HeLa cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings. Thus, human telomerase is a critical enzyme for the long-term proliferation of immortal tumor cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feng, J -- Funk, W D -- Wang, S S -- Weinrich, S L -- Avilion, A A -- Chiu, C P -- Adams, R R -- Chang, E -- Allsopp, R C -- Yu, J -- AG09383/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 1995 Sep 1;269(5228):1236-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geron Corporation, Menlo Park, CA 94025, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7544491" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Death ; *Cell Division ; Cell Line ; Cloning, Molecular ; DNA Nucleotidylexotransferase/antagonists & ; inhibitors/chemistry/genetics/*metabolism ; HeLa Cells ; Humans ; Molecular Sequence Data ; Oligonucleotides, Antisense/pharmacology ; Polymerase Chain Reaction ; RNA/chemistry/genetics/*metabolism ; Templates, Genetic ; Transfection ; Tumor Cells, Cultured
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  • 4
    Publication Date: 1995-11-03
    Description: The human beta-globin locus control region (LCR) controls the transcription, chromatin structure, and replication timing of the entire locus. DNA replication was found to initiate in a transcription-independent manner within a region located 50 kilobases downstream of the LCR in human, mouse, and chicken cells containing the entire human beta-globin locus. However, DNA replication did not initiate within a deletion mutant locus lacking the sequences that encompass the LCR. This mutant locus replicated in the 3' to 5' direction. Thus, interactions between distantly separated sequences can be required for replication initiation, and factors mediating this interaction appear to be conserved in evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aladjem, M I -- Groudine, M -- Brody, L L -- Dieken, E S -- Fournier, R E -- Wahl, G M -- Epner, E M -- New York, N.Y. -- Science. 1995 Nov 3;270(5237):815-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Salk Institute, San Diego, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481774" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Biological Evolution ; Cell Line ; Chickens ; *DNA Replication ; Globins/*genetics ; Humans ; Hybrid Cells ; Mice ; Molecular Sequence Data ; *Regulatory Sequences, Nucleic Acid ; Sequence Deletion ; Tumor Cells, Cultured
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  • 5
    Publication Date: 1995-03-10
    Description: The crystal structure of the tungsten-containing aldehyde ferredoxin oxidoreductase (AOR) from Pyrococcus furiosus, a hyperthermophilic archaeon (formerly archaebacterium) that grows optimally at 100 degrees C, has been determined at 2.3 angstrom resolution by means of multiple isomorphous replacement and multiple crystal form averaging. AOR consists of two identical subunits, each containing an Fe4S4 cluster and a molybdopterin-based tungsten cofactor that is analogous to the molybdenum cofactor found in a large class of oxotransferases. Whereas the general features of the tungsten coordination in this cofactor were consistent with a previously proposed structure, each AOR subunit unexpectedly contained two molybdopterin molecules that coordinate a tungsten by a total of four sulfur ligands, and the pterin system was modified by an intramolecular cyclization that generated a three-ringed structure. In comparison to other proteins, the hyperthermophilic enzyme AOR has a relatively small solvent-exposed surface area, and a relatively large number of both ion pairs and buried atoms. These properties may contribute to the extreme thermostability of this enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chan, M K -- Mukund, S -- Kletzin, A -- Adams, M W -- Rees, D C -- 1F32 GM15006/GM/NIGMS NIH HHS/ -- GM50775/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Mar 10;267(5203):1463-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, Pasadena, CA 91125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7878465" target="_blank"〉PubMed〈/a〉
    Keywords: Aldehyde Oxidoreductases/*chemistry/metabolism ; Amino Acid Sequence ; Archaea/*enzymology ; Binding Sites ; *Coenzymes ; Computer Graphics ; Crystallography, X-Ray ; Enzyme Stability ; Ferrous Compounds ; Metalloproteins/analysis/chemistry ; Models, Molecular ; Molecular Sequence Data ; Organometallic Compounds/analysis/*chemistry ; Oxidation-Reduction ; Protein Conformation ; Protein Structure, Secondary ; Pteridines/analysis/chemistry ; Pterins/analysis/*chemistry ; Surface Properties ; Temperature ; Tungsten/analysis/*chemistry
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  • 6
    Publication Date: 1995-03-31
    Description: Members of the interleukin-6 family of cytokines bind to and activate receptors that contain a common subunit, gp130. This leads to the activation of Stat3 and Stat1, two cytoplasmic signal transducers and activators of transcription (STATs), by tyrosine phosphorylation. Serine phosphorylation of Stat3 was constitutive and was enhanced by signaling through gp130. In cells of lymphoid and neuronal origins, inhibition of serine phosphorylation prevented the formation of complexes of DNA with Stat3-Stat3 but not with Stat3-Stat1 or Stat1-Stat1 dimers. In vitro serine dephosphorylation of Stat3 also inhibited DNA binding of Stat3-Stat3. The requirement of serine phosphorylation for Stat3-Stat3.DNA complex formation was inversely correlated with the affinity of Stat3-Stat3 for the binding site. Thus, serine phosphorylation appears to enhance or to be required for the formation of stable Stat3-Stat3.DNA complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, X -- Blenis, J -- Li, H C -- Schindler, C -- Chen-Kiang, S -- CA46595/CA/NCI NIH HHS/ -- HL 21006/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1995 Mar 31;267(5206):1990-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7701321" target="_blank"〉PubMed〈/a〉
    Keywords: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Cell Nucleus/metabolism ; Ciliary Neurotrophic Factor ; Cytoplasm/metabolism ; DNA/metabolism ; DNA-Binding Proteins/*metabolism ; Humans ; Interleukin-6/metabolism/*pharmacology ; Isoquinolines/pharmacology ; Mice ; Molecular Sequence Data ; Nerve Tissue Proteins/pharmacology ; Phosphorylation ; Piperazines/pharmacology ; *Promoter Regions, Genetic ; STAT1 Transcription Factor ; STAT3 Transcription Factor ; Serine/*metabolism ; Signal Transduction ; Threonine/metabolism ; Trans-Activators/*metabolism ; Tumor Cells, Cultured ; Tyrosine/metabolism
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-12-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, P B -- New York, N.Y. -- Science. 1995 Dec 1;270(5241):1453-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Yale University, New Haven, CT 05620-8107, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7491488" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; GTP Phosphohydrolase-Linked Elongation Factors/metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; *Molecular Mimicry ; Peptide Chain Elongation, Translational ; Peptide Elongation Factor G ; Peptide Elongation Factor Tu/*chemistry/metabolism ; Peptide Elongation Factors/*chemistry/metabolism ; *Protein Biosynthesis ; RNA, Transfer/*chemistry/metabolism ; RNA, Transfer, Amino Acyl/metabolism ; Ribosomes/metabolism
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  • 8
    Publication Date: 1995-06-09
    Description: Kidney bean purple acid phosphatase (KBPAP) is an Fe(III)-Zn(II) metalloenzyme resembling the mammalian Fe(III)-Fe(II) purple acid phosphatases. The structure of the homodimeric 111-kilodalton KBPAP was determined at a resolution of 2.9 angstroms. The enzyme contains two domains in each subunit. The active site is located in the carboxyl-terminal domain at the carboxy end of two sandwiched beta alpha beta alpha beta motifs. The two metal ions are 3.1 angstroms apart and bridged monodentately by Asp164. The iron is further coordinated by Tyr167, His325, and Asp135, and the zinc by His286, His323, and Asn201. The active-site structure is consistent with previous proposals regarding the mechanism of phosphate ester hydrolysis involving nucleophilic attack on the phosphate group by an Fe(III)-coordinated hydroxide ion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Strater, N -- Klabunde, T -- Tucker, P -- Witzel, H -- Krebs, B -- New York, N.Y. -- Science. 1995 Jun 9;268(5216):1489-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Anorganisch-Chemisches Institut, Universitat Munster, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7770774" target="_blank"〉PubMed〈/a〉
    Keywords: Acid Phosphatase/*chemistry/metabolism ; Binding Sites ; Computer Graphics ; Crystallography, X-Ray ; Fabaceae/enzymology ; Ferric Compounds/chemistry/metabolism ; Glycoproteins/*chemistry/metabolism ; Ligands ; Models, Molecular ; Plants, Medicinal ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Zinc/chemistry/metabolism
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-02-03
    Description: The guanine-uracil (G.U) base pair that helps to define the 5'-splice site of group I introns is phylogenetically highly conserved. In such a wobble base pair, G makes two hydrogen bonds with U in a geometry shifted from that of a canonical Watson-Crick pair. The contribution made by individual functional groups of the G.U pair in the context of the Tetrahymena ribozyme was examined by replacement of the G.U pair with synthetic base pairs that maintain a wobble configuration, but that systematically alter functional groups in the major and minor grooves of the duplex. The substitutions demonstrate that the exocyclic amine of G, when presented on the minor groove surface by the wobble base pair conformation, contributes substantially (2 kilocalories.mole-1) to binding by making a tertiary interaction with the ribozyme active site. It contributes additionally to transition state stabilization. The ribozyme active site also makes tertiary contacts with a tripod of 2'-hydroxyls on the minor groove surface of the splice site helix. This suggests that the ribozyme binds the duplex primarily in the minor groove. The alanyl aminoacyl transfer RNA (tRNA) synthetase recognizes the exocyclic amine of an invariant G.U pair and contacts a similar array of 2'-hydroxyls when binding the tRNA(Ala) acceptor stem, providing an unanticipated parallel between protein-RNA and RNA-RNA interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Strobel, S A -- Cech, T R -- New York, N.Y. -- Science. 1995 Feb 3;267(5198):675-9.〈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/7839142" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Base Sequence ; Binding Sites ; Exons ; Guanine/chemistry/*metabolism ; Guanosine Monophosphate/metabolism ; Hydrogen Bonding ; Introns ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Oligoribonucleotides/*metabolism ; RNA Splicing ; RNA, Catalytic/chemistry/*metabolism ; Tetrahymena/enzymology ; Uracil/chemistry/*metabolism
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  • 10
    Publication Date: 1995-12-22
    Description: A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hudson, T J -- Stein, L D -- Gerety, S S -- Ma, J -- Castle, A B -- Silva, J -- Slonim, D K -- Baptista, R -- Kruglyak, L -- Xu, S H -- Hu, X -- Colbert, A M -- Rosenberg, C -- Reeve-Daly, M P -- Rozen, S -- Hui, L -- Wu, X -- Vestergaard, C -- Wilson, K M -- Bae, J S -- Maitra, S -- Ganiatsas, S -- Evans, C A -- DeAngelis, M M -- Ingalls, K A -- Nahf, R W -- Horton, L T Jr -- Anderson, M O -- Collymore, A J -- Ye, W -- Kouyoumjian, V -- Zemsteva, I S -- Tam, J -- Devine, R -- Courtney, D F -- Renaud, M T -- Nguyen, H -- O'Connor, T J -- Fizames, C -- Faure, S -- Gyapay, G -- Dib, C -- Morissette, J -- Orlin, J B -- Birren, B W -- Goodman, N -- Weissenbach, J -- Hawkins, T L -- Foote, S -- Page, D C -- Lander, E S -- HG00017/HG/NHGRI NIH HHS/ -- HG00098/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 1995 Dec 22;270(5244):1945-54.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead-MIT Center for Genome Research, Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8533086" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Chromosome Mapping ; Chromosomes, Artificial, Yeast ; Databases, Factual ; Gene Expression ; Genetic Markers ; *Genome, Human ; *Human Genome Project ; Humans ; Hybrid Cells ; Polymerase Chain Reaction ; *Sequence Analysis, DNA ; *Sequence Tagged Sites
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  • 11
    Publication Date: 1995-05-26
    Description: Receptor-mediated activation of heterotrimeric guanine nucleotide-binding proteins (G proteins) results in the dissociation of alpha from beta gamma subunits, thereby allowing both to regulate effectors. Little is known about the regions of effectors required for recognition of G beta gamma. A peptide encoding residues 956 to 982 of adenylyl cyclase 2 specifically blocked G beta gamma stimulation of adenylyl cyclase 2, phospholipase C-beta 3, potassium channels, and beta-adrenergic receptor kinase as well as inhibition of calmodulin-stimulated adenylyl cyclases, but had no effect on interactions between G beta gamma and G alpha o. Substitutions in this peptide identified a functionally important motif, Gln-X-X-Glu-Arg, that is also conserved in regions of potassium channels and beta-adrenergic receptor kinases that participate in G beta gamma interactions. Thus, the region defined by residues 956 to 982 of adenylyl cyclase 2 may contain determinants important for receiving signals from G beta gamma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, J -- DeVivo, M -- Dingus, J -- Harry, A -- Li, J -- Sui, J -- Carty, D J -- Blank, J L -- Exton, J H -- Stoffel, R H -- CA-44998/CA/NCI NIH HHS/ -- DK-37219/DK/NIDDK NIH HHS/ -- DK-38761/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1995 May 26;268(5214):1166-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, NY 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7761832" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclase Inhibitors ; Adenylyl Cyclases/*chemistry/metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Enzyme Activation/physiology ; GTP-Binding Proteins/chemistry/*physiology ; Guanosine Triphosphate/physiology ; In Vitro Techniques ; Molecular Sequence Data ; Peptide Fragments/chemical synthesis/chemistry/physiology ; Potassium Channels/physiology ; Rats ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, Adrenergic, beta/metabolism ; Signal Transduction/physiology ; Structure-Activity Relationship ; Type C Phospholipases/metabolism
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  • 12
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-09-08
    Description: TNF receptor-associated factor (TRAF) proteins are candidate signal transducers that associate with the cytoplasmic domains of members of the tumor necrosis factor (TNF) receptor superfamily. The role of TRAFs in the TNF-R2 and CD40 signal transduction pathways, which result in the activation of transcription factor NF-kappa B, was investigated. Overexpression of TRAF2, but not TRAF1 or TRAF3, was sufficient to induce NF-kappa B activation. A truncated derivative of TRAF2 lacking an amino-terminal RING finger domain was a dominant-negative inhibitor of NF-kappa B activation mediated by TNF-R2 and CD40. Thus, TRAF2 is a common mediator of TNF-R2 and CD40 signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rothe, M -- Sarma, V -- Dixit, V M -- Goeddel, D V -- CA64803/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1995 Sep 8;269(5229):1424-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Department, Tularik, Inc., South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7544915" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/*metabolism ; Antigens, CD40 ; Antigens, Differentiation, B-Lymphocyte/*metabolism ; Cell Line ; Gene Expression Regulation ; Genes, Reporter ; Mice ; NF-kappa B/*metabolism ; Proteins/*metabolism ; Receptors, Tumor Necrosis Factor/*metabolism ; Receptors, Tumor Necrosis Factor, Type I ; Receptors, Tumor Necrosis Factor, Type II ; *Signal Transduction ; T-Lymphocytes/metabolism ; TNF Receptor-Associated Factor 2 ; Transfection
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  • 13
    Publication Date: 1995-08-11
    Description: In the molecular scheme of living organisms, adenosine 3',5'-monophosphate (cyclic AMP or cAMP) has been a universal second messenger. In eukaryotic cells, the primary receptors for cAMP are the regulatory subunits of cAMP-dependent protein kinase. The crystal structure of a 1-91 deletion mutant of the type I alpha regulatory subunit was refined to 2.8 A resolution. Each of the two tandem cAMP binding domains provides an extensive network of hydrogen bonds that buries the cyclic phosphate and the ribose between two beta strands that are linked by a short alpha helix. Each adenine base stacks against an aromatic ring that lies outside the beta barrel. This structure provides a molecular basis for understanding how cAMP binds cooperatively to its receptor protein, thus mediating activation of the kinase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Su, Y -- Dostmann, W R -- Herberg, F W -- Durick, K -- Xuong, N H -- Ten Eyck, L -- Taylor, S S -- Varughese, K I -- GM07313/GM/NIGMS NIH HHS/ -- GM34921/GM/NIGMS NIH HHS/ -- RR01644/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1995 Aug 11;269(5225):807-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093-0654, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7638597" target="_blank"〉PubMed〈/a〉
    Keywords: Affinity Labels ; Amino Acid Sequence ; Binding Sites ; Carrier Proteins/*chemistry/genetics/metabolism ; Computer Graphics ; Crystallization ; Crystallography, X-Ray ; Cyclic AMP/analogs & derivatives/*metabolism ; Cyclic AMP-Dependent Protein Kinases/*chemistry ; Enzyme Activation ; Hydrogen Bonding ; *Intracellular Signaling Peptides and Proteins ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 14
    Publication Date: 1995-11-03
    Description: The BRCA1 gene product was identified as a 220-kilodalton nuclear phosphoprotein in normal cells, including breast ductal epithelial cells, and in 18 of 20 tumor cell lines derived from tissues other than breast and ovary. In 16 of 17 breast and ovarian cancer lines and 17 of 17 samples of cells obtained from malignant effusions, however, BRCA1 localized mainly in cytoplasm. Absence of BRCA1 or aberrant subcellular location was also observed to a variable extent in histological sections of many breast cancer biopsies. These findings suggest that BRCA1 abnormalities may be involved in the pathogenesis of many breast cancers, sporadic as well as familial.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Y -- Chen, C F -- Riley, D J -- Allred, D C -- Chen, P L -- Von Hoff, D -- Osborne, C K -- Lee, W H -- CA58318/CA/NCI NIH HHS/ -- EY05758/EY/NEI NIH HHS/ -- P50CA58183/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1995 Nov 3;270(5237):789-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Medicine/Institute of Biotechnology, University of Texas Health Science Center at San Antonio 78245, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481765" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; BRCA1 Protein ; Base Sequence ; Breast/*chemistry ; Breast Neoplasms/*chemistry/ultrastructure ; Cell Fractionation ; Cell Line ; Cell Nucleus/chemistry ; Cytoplasm/*chemistry ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Neoplasm Proteins/*analysis/genetics/metabolism ; Neoplasms/chemistry/ultrastructure ; Ovarian Neoplasms/chemistry/ultrastructure ; Pleural Effusion, Malignant/chemistry/pathology ; Transcription Factors/*analysis/genetics/metabolism ; Tumor Cells, Cultured
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  • 15
    Publication Date: 1995-08-11
    Description: Cystic fibrosis transmembrane regulator (CFTR), the gene product that is mutated in cystic fibrosis (CF) patients, has a well-recognized function as a cyclic adenosine 3',5'-monophosphate (cAMP)-regulated chloride channel, but this property does not account for the abnormally high basal rate and cAMP sensitivity of sodium ion absorption in CF airway epithelia. Expression of complementary DNAs for rat epithelial Na+ channel (rENaC) alone in Madin Darby canine kidney (MDCK) epithelial cells generated large amiloride-sensitive sodium currents that were stimulated by cAMP, whereas coexpression of human CFTR with rENaC generated smaller basal sodium currents that were inhibited by cAMP. Parallel studies that measured regulation of sodium permeability in fibroblasts showed similar results. In CF airway epithelia, the absence of this second function of CFTR as a cAMP-dependent regulator likely accounts for abnormal sodium transport.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stutts, M J -- Canessa, C M -- Olsen, J C -- Hamrick, M -- Cohn, J A -- Rossier, B C -- Boucher, R C -- CFF R026/PHS HHS/ -- HL 34322/HL/NHLBI NIH HHS/ -- HL 42384/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1995 Aug 11;269(5225):847-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill 27599-7020, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7543698" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Absorption ; Amiloride/pharmacology ; Animals ; Cell Line ; Cell Membrane Permeability ; Chloride Channels/metabolism ; Cyclic AMP/*metabolism ; Cystic Fibrosis/*metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator ; DNA, Complementary ; Dogs ; Humans ; Membrane Proteins/*metabolism ; Mice ; Patch-Clamp Techniques ; Rats ; Sodium/metabolism ; Sodium Channels/*metabolism ; Transfection
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  • 16
    Publication Date: 1995-06-23
    Description: The rate-limiting step in cholesterol biosynthesis in mammals is catalyzed by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a four-electron oxidoreductase that converts HMG-CoA to mevalonate. The crystal structure of HMG-CoA reductase from Pseudomonas mevalonii was determined at 3.0 angstrom resolution by multiple isomorphous replacement. The structure reveals a tightly bound dimer that brings together at the subunit interface the conserved residues implicated in substrate binding and catalysis. These dimers are packed about a threefold crystallographic axis, forming a hexamer with 23 point group symmetry. Difference Fourier studies reveal the binding sites for the substrates HMG-CoA and reduced or oxidized nicotinamide adenine dinucleotide [NAD(H)] and demonstrate that the active sites are at the dimer interfaces. The HMG-CoA is bound by a domain with an unusual fold, consisting of a central alpha helix surrounded by a triangular set of walls of beta sheets and alpha helices. The NAD(H) is bound by a domain characterized by an antiparallel beta structure that defines a class of dinucleotide-binding domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawrence, C M -- Rodwell, V W -- Stauffacher, C V -- AI 127713/AI/NIAID NIH HHS/ -- HL 47113/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1995 Jun 23;268(5218):1758-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7792601" target="_blank"〉PubMed〈/a〉
    Keywords: Acyl Coenzyme A/metabolism ; Amino Acid Sequence ; Binding Sites ; Computer Graphics ; Crystallography, X-Ray ; Fourier Analysis ; Hydroxymethylglutaryl CoA Reductases/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; NAD/metabolism ; Protein Folding ; Protein Structure, Secondary ; Pseudomonas/*enzymology
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  • 17
    Publication Date: 1995-08-18
    Description: The relative orientations of carbon monoxide (CO) bound to and photodissociated from myoglobin in solution have been determined with time-resolved infrared polarization spectroscopy. The bound CO is oriented 〈 or = 7 degrees from the heme normal, corresponding to nearly linear FE-C-O. Upon dissociation from the Fe, CO becomes trapped in a docking site that orientationally constrains it to lie approximately in the plane of the heme. Because the bound and "docked" CO are oriented in nearly orthogonal directions CO binding from the docking site is suppressed. These solutions results help to establish how myoglobin discriminates against CO, a controversial issue dominated by the misconception that Fe-C-O is bent.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lim, M -- Jackson, T A -- Anfinrud, P A -- DK45306/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1995 Aug 18;269(5226):962-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Harvard University, Cambridge, MA 02138 USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7638619" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Carbon Monoxide/*chemistry/metabolism ; Crystallography, X-Ray ; Ligands ; Light ; Myoglobin/*chemistry/metabolism ; Oxygen/chemistry/metabolism ; Photolysis ; Protein Conformation ; Spectrophotometry, Infrared ; Temperature
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  • 18
    Publication Date: 1995-03-10
    Description: RNA encoding the B subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptor (GluR-B) undergoes a posttranscriptional modification in which a genomically encoded adenosine is represented as a guanosine in the GluR-B complementary DNA. In vitro editing of GluR-B RNA transcripts with HeLa cell nuclear extracts was found to result from an activity that converts adenosine to inosine in regions of double-stranded RNA by enzymatic base modification. This activity is consistent with that of a double-stranded RNA-specific adenosine deaminase previously described in Xenopus oocytes and widely distributed in mammalian tissues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rueter, S M -- Burns, C M -- Coode, S A -- Mookherjee, P -- Emeson, R B -- ES00267/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1995 Mar 10;267(5203):1491-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-6600.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7878468" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/*metabolism ; Animals ; Base Sequence ; Cell Line ; Codon ; Exons ; HeLa Cells ; Humans ; Inosine/*metabolism ; Inosine Monophosphate/metabolism ; Mice ; Molecular Sequence Data ; *RNA Editing ; RNA Precursors/metabolism ; RNA, Double-Stranded/metabolism ; Rats ; Receptors, AMPA/*genetics ; Repetitive Sequences, Nucleic Acid ; Tumor Cells, Cultured
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  • 19
    Publication Date: 1995-11-17
    Description: A member of the inwardly rectifying potassium channel family was cloned here. The channel, called BIR (Kir6.2), was expressed in large amounts in rat pancreatic islets and glucose-responsive insulin-secreting cell lines. Coexpression with the sulfonylurea receptor SUR reconstituted an inwardly rectifying potassium conductance of 76 picosiemens that was sensitive to adenosine triphosphate (ATP) (IKATP) and was inhibited by sulfonylureas and activated by diazoxide. The data indicate that these pancreatic beta cell potassium channels are a complex composed of at least two subunits--BIR, a member of the inward rectifier potassium channel family, and SUR, a member of the ATP-binding cassette superfamily. Gene mapping data show that these two potassium channel subunit genes are clustered on human chromosome 11 at position 11p15.1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Inagaki, N -- Gonoi, T -- Clement, J P 4th -- Namba, N -- Inazawa, J -- Gonzalez, G -- Aguilar-Bryan, L -- Seino, S -- Bryan, J -- DK44311/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1995 Nov 17;270(5239):1166-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Medicine, Chiba University School of Medicine, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7502040" target="_blank"〉PubMed〈/a〉
    Keywords: *ATP-Binding Cassette Transporters ; Adenosine Triphosphate/pharmacology ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Chromosome Mapping ; Chromosomes, Human, Pair 11 ; Cloning, Molecular ; Cricetinae ; Diazoxide/pharmacology ; Humans ; Islets of Langerhans/metabolism ; KATP Channels ; Mice ; Molecular Sequence Data ; Potassium/*metabolism ; Potassium Channels/*chemistry/genetics/*metabolism ; *Potassium Channels, Inwardly Rectifying ; Rats ; Receptors, Drug/*chemistry/metabolism ; Rubidium/metabolism ; Sulfonylurea Compounds/pharmacology ; Sulfonylurea Receptors
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldberg, A L -- New York, N.Y. -- Science. 1995 Apr 28;268(5210):522-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7725095" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Archaeal Proteins ; Binding Sites ; Crystallography, X-Ray ; Cysteine Endopeptidases/chemistry/*metabolism ; Endopeptidases/chemistry/*metabolism ; Humans ; Hydrolysis ; Multienzyme Complexes/chemistry/*metabolism ; Proteasome Endopeptidase Complex ; Proteins/*metabolism ; Thermoplasma/enzymology ; Ubiquitins/metabolism
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  • 21
    Publication Date: 1995-08-25
    Description: The high resolution three-dimensional x-ray structure of the metal sites of bovine heart cytochrome c oxidase is reported. Cytochrome c oxidase is the largest membrane protein yet crystallized and analyzed at atomic resolution. Electron density distribution of the oxidized bovine cytochrome c oxidase at 2.8 A resolution indicates a dinuclear copper center with an unexpected structure similar to a [2Fe-2S]-type iron-sulfur center. Previously predicted zinc and magnesium sites have been located, the former bound by a nuclear encoded subunit on the matrix side of the membrane, and the latter situated between heme a3 and CuA, at the interface of subunits I and II. The O2 binding site contains heme a3 iron and copper atoms (CuB) with an interatomic distance of 4.5 A; there is no detectable bridging ligand between iron and copper atoms in spite of a strong antiferromagnetic coupling between them. A hydrogen bond is present between a hydroxyl group of the hydroxyfarnesylethyl side chain of heme a3 and an OH of a tyrosine. The tyrosine phenol plane is immediately adjacent and perpendicular to an imidazole group bonded to CuB, suggesting a possible role in intramolecular electron transfer or conformational control, the latter of which could induce the redox-coupled proton pumping. A phenyl group located halfway between a pyrrole plane of the heme a3 and an imidazole plane liganded to the other heme (heme a) could also influence electron transfer or conformational control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsukihara, T -- Aoyama, H -- Yamashita, E -- Tomizaki, T -- Yamaguchi, H -- Shinzawa-Itoh, K -- Nakashima, R -- Yaono, R -- Yoshikawa, S -- New York, N.Y. -- Science. 1995 Aug 25;269(5227):1069-74.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Protein Research, Osaka University, Suita, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7652554" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cattle ; Copper/*analysis ; Crystallization ; Crystallography, X-Ray ; Electron Transport ; Electron Transport Complex IV/*chemistry/metabolism ; Fourier Analysis ; Heme/*analogs & derivatives/analysis ; Hydrogen Bonding ; Magnesium/*analysis ; Mitochondria, Heart/enzymology ; Models, Molecular ; Oxidation-Reduction ; Oxygen/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Proton Pumps ; Zinc/*analysis
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  • 22
    Publication Date: 1995-04-21
    Description: Fibroblast growth factors (FGFs) require a polysaccharide cofactor, heparin or heparan sulfate (HS), for receptor binding and activation. To probe the molecular mechanism by which heparin or HS (heparin/HS) activates FGF, small nonsulfated oligosaccharides found within heparin/HS were assayed for activity. These synthetic and isomerically pure compounds can activate the FGF signaling pathway. The crystal structures of complexes between FGF and these heparin/HS oligosaccharides reveal several binding sites on FGF and constrain possible mechanisms by which heparin/HS can activate the FGF receptor. These studies establish a framework for the molecular design of compounds capable of modulating FGF activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ornitz, D M -- Herr, A B -- Nilsson, M -- Westman, J -- Svahn, C M -- Waksman, G -- CA60673/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1995 Apr 21;268(5209):432-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7536345" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Carbohydrate Sequence ; Cell Line ; Crystallization ; Fibroblast Growth Factor 1/chemistry/*metabolism ; Fibroblast Growth Factor 2/*metabolism ; Heparin/metabolism/*pharmacology ; Heparitin Sulfate/chemistry/*pharmacology ; Mitogens/pharmacology ; Molecular Sequence Data ; Oligosaccharides/chemistry/metabolism/*pharmacology ; Receptors, Fibroblast Growth Factor/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction
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  • 23
    Publication Date: 1995-04-14
    Description: The mammalian growth factor receptor-binding protein Grb2 is an adaptor that mediates activation of guanine nucleotide exchange on Ras. Grb2 binds to the receptor through its SH2 domain and to the carboxyl-terminal domain of Son of sevenless through its two SH3 domains. It is thus a key element in the signal transduction pathway. The crystal structure of Grb2 was determined to 3.1 angstrom resolution. The asymmetric unit is composed of an embedded dimer. The interlaced junctions between the SH2 and SH3 domains bring the two adjacent faces of the SH3 domains in van der Waals contact but leave room for the binding of proline-rich peptides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maignan, S -- Guilloteau, J P -- Fromage, N -- Arnoux, B -- Becquart, J -- Ducruix, A -- New York, N.Y. -- Science. 1995 Apr 14;268(5208):291-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Biologie Structurale, Unite Mixte de Recherche CNRS-Universite de Paris-Sud, Gif sur Yvette, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7716522" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Binding Sites ; Computer Graphics ; Crystallization ; Crystallography, X-Ray ; GRB2 Adaptor Protein ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Secondary ; Proteins/*chemistry/metabolism ; *Receptor, Epidermal Growth Factor/metabolism
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-01-13
    Description: Previous studies suggest that the mechanism of action of the ribosome in translation involves crucial transfer RNA (tRNA)-ribosomal RNA (rRNA) interactions. Here, a selection scheme was developed to identify bases in 16S rRNA that are essential for tRNA binding to the P site of the small (30S) ribosomal subunit. Modification of the N-1 and N-2 positions of 2-methylguanine 966 and of the N-7 position of guanine 1401 interfered with messenger RNA (mRNA)-dependent binding of tRNA to the P site. Modification of the same positions as well as of the N-1 and N-2 positions of guanine 926 interfered with mRNA-independent binding of tRNA at high magnesium ion concentration. These results suggest that these three bases are involved in intermolecular contacts between ribosomes and tRNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von Ahsen, U -- Noller, H F -- GM17129/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Jan 13;267(5195):234-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sinsheimer Laboratories, University of California, Santa Cruz 95064.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7528943" target="_blank"〉PubMed〈/a〉
    Keywords: Aldehydes/pharmacology ; Base Composition ; Binding Sites ; CME-Carbodiimide/analogs & derivatives/pharmacology ; Codon ; Guanine/chemistry ; Nucleic Acid Conformation ; RNA, Bacterial/chemistry/metabolism ; RNA, Messenger/metabolism ; RNA, Ribosomal, 16S/*chemistry/metabolism ; RNA, Transfer, Leu/*metabolism ; RNA, Transfer, Phe/*metabolism ; Ribosomes/*metabolism ; Sulfides/pharmacology
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  • 25
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-10-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kovacs, J A -- Shoner, S C -- Ellison, J J -- New York, N.Y. -- Science. 1995 Oct 27;270(5236):587-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Washington, Seattle 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7570015" target="_blank"〉PubMed〈/a〉
    Keywords: Aldehyde Oxidoreductases/*chemistry/metabolism ; Binding Sites ; Carbon/chemistry ; Carbon Monoxide/metabolism ; Electrons ; Iron-Sulfur Proteins/*chemistry/metabolism ; Ligands ; Metalloproteins/*chemistry/metabolism ; *Multienzyme Complexes ; Nickel/chemistry ; Oxidation-Reduction
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  • 26
    Publication Date: 1995-02-17
    Description: Although the myogenic regulator MyoD is expressed in proliferating myoblasts, differentiation of these cells is limited to the G0 phase of the cell cycle. Forced expression of cyclin D1, but not cyclins A, B, or E, inhibited the ability of MyoD to transactivate muscle-specific genes and correlated with phosphorylation of MyoD. Transfection of myoblasts with cyclin-dependent kinase (Cdk) inhibitors p21 and p16 augmented muscle-specific gene expression in cells maintained in high concentrations of serum, suggesting that an active cyclin-Cdk complex suppresses MyoD function in proliferating cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Skapek, S X -- Rhee, J -- Spicer, D B -- Lassar, A B -- 1F32AR08214-01A1/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Feb 17;267(5200):1022-4.〈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/7863328" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carrier Proteins/biosynthesis/physiology ; Cell Cycle ; Cell Differentiation ; Cell Line ; Cyclin D1 ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinases/*metabolism ; Cyclins/biosynthesis/*physiology ; Enzyme Activation ; Mice ; Muscle, Skeletal/*cytology/metabolism ; MyoD Protein/*antagonists & inhibitors/metabolism ; Oncogene Proteins/*physiology ; Phosphorylation ; Transcriptional Activation ; Transfection
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  • 27
    Publication Date: 1995-09-22
    Description: The behavioral and cognitive effects of nicotine suggest that nicotinic acetylcholine receptors (nAChRs) participate in central nervous system (CNS) function. Although nAChR subunit messenger RNA (mRNA) and nicotine binding sites are common in the brain, there is little evidence for synapses mediated by nAChRs in the CNS. To test whether, CNS nAChRs might modify rather than mediate transmission, the regulation of excitatory synaptic transmission by these receptors was examined. Nanomolar concentrations of nicotine enhanced both glutamatergic and cholinergic synaptic transmission by activation of presynaptic nAChRs that increased presynaptic [Ca2]i. Pharmacological and subunit deletion experiments reveal that these presynaptic nAChRs include the alpha 7 subunit. These findings reveal that CNS nAChRs enhance fast excitatory transmission, providing a likely mechanism for the complex behavioral effects of nicotine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGehee, D S -- Heath, M J -- Gelber, S -- Devay, P -- Role, L W -- NS09395/NS/NINDS NIH HHS/ -- NS22061/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1995 Sep 22;269(5231):1692-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Anatomy, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569895" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Brain/drug effects/*physiology ; Bungarotoxins/metabolism/pharmacology ; Calcium/physiology ; Chick Embryo ; Culture Techniques ; Ganglia, Sympathetic/drug effects/physiology ; Glutamic Acid/metabolism ; Molecular Sequence Data ; Nicotine/metabolism/*pharmacology ; Nicotinic Agonists/metabolism/*pharmacology ; Presynaptic Terminals/chemistry/drug effects/*physiology ; Receptors, Nicotinic/analysis/*physiology ; Synapses/drug effects/physiology ; Synaptic Transmission/*drug effects ; Thalamic Nuclei/drug effects/physiology
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  • 28
    Publication Date: 1995-03-03
    Description: Many members of the cytokine receptor superfamily initiate intracellular signaling by activating members of the Jak family of tyrosine kinases. Activation of the same Jaks by multiple cytokines raises the question of how these cytokines activate distinct intracellular signaling pathways. Selection of particular substrates--the transcriptional activator Stat3 and protein tyrosine phosphatase PTP1D--that characterize responses to the ciliary neurotrophic factor-interleukin-6 cytokine family depended not on which Jak was activated, but was instead determined by specific tyrosine-based motifs in the receptor components--gp130 and LIFR--shared by these cytokines. Further, these tyrosine-based motifs were modular, because addition of a Stat3-specifying motif to another cytokine receptor, that for erythropoietin, caused it to activate Stat3 in a ligand-dependent fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stahl, N -- Farruggella, T J -- Boulton, T G -- Zhong, Z -- Darnell, J E Jr -- Yancopoulos, G D -- New York, N.Y. -- Science. 1995 Mar 3;267(5202):1349-53.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7871433" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Antigens, CD ; Cell Line ; Cytokine Receptor gp130 ; DNA-Binding Proteins/*metabolism ; *Growth Inhibitors ; Interleukin-6/pharmacology ; Intracellular Signaling Peptides and Proteins ; Leukemia Inhibitory Factor ; *Lymphokines ; Membrane Glycoproteins/chemistry/*metabolism ; Molecular Sequence Data ; Phosphorylation ; Point Mutation ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/metabolism ; Protein-Tyrosine Kinases/*metabolism ; Receptors, Cytokine/chemistry/*metabolism ; Receptors, OSM-LIF ; Recombinant Fusion Proteins/metabolism ; STAT3 Transcription Factor ; *Signal Transduction ; Trans-Activators/*metabolism ; Tyrosine/metabolism
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  • 29
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-12-15
    Description: For almost 200 years inert antigens have been used for initiating the process of immunization. A procedure is now described in which the antigen used is so highly reactive that a chemical reaction occurs in the antibody combining site during immunization. An organophosphorus diester hapten was used to illustrate this concept coined "reactive immunization." The organophosphonate recruited chemical potential from the immune response that resembled the way these compounds recruit the catalytic power of the serine hydrolases. During this recruitment, a large proportion of the isolated antibodies catalyzed the formation and cleavage of phosphonylated intermediates and subsequent ester hydrolysis. Reactive immunization can augment traditional immunization and enhance the scope of catalytic antibody chemistry. Among the compounds anticipated to be effective are those that contain appropriate reactive functionalities or those that are latently reactive, as in the mechanism-based inhibitors of enzymes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wirsching, P -- Ashley, J A -- Lo, C H -- Janda, K D -- Lerner, R A -- DA08590/DA/NIDA NIH HHS/ -- GM48351/GM/NIGMS NIH HHS/ -- P01 CA27489-16/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1995 Dec 15;270(5243):1775-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Scripps Research Institute, Department of Molecular Biology, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8525366" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Catalytic/*chemistry/immunology ; Antibodies, Monoclonal/chemistry/immunology ; Antigen-Antibody Reactions ; Antigens/*chemistry/immunology ; Binding Sites ; Catalysis ; Cattle ; Esters/chemistry/immunology ; Haptens/chemistry/immunology ; Immunization/*methods ; Kinetics ; Mice ; Organophosphonates/chemistry/*immunology ; Thermodynamics ; Tumor Cells, Cultured
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  • 30
    Publication Date: 1995-09-01
    Description: A mutated cyclin-dependent kinase 4 (CDK4) was identified as a tumor-specific antigen recognized by HLA-A2. 1-restricted autologous cytolytic T lymphocytes (CTLs) in a human melanoma. The mutated CDK4 allele was present in autologous cultured melanoma cells and metastasis tissue, but not in the patient's lymphocytes. The mutation, an arginine-to-cysteine exchange at residue 24, was part of the CDK4 peptide recognized by CTLs and prevented binding of the CDK4 inhibitor p16INK4a, but not of p21 or of p27KIP1. The same mutation was found in one additional melanoma among 28 melanomas analyzed. These results suggest that mutation of CDK4 can create a tumor-specific antigen and can disrupt the cell-cycle regulation exerted by the tumor suppressor p16INK4a.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolfel, T -- Hauer, M -- Schneider, J -- Serrano, M -- Wolfel, C -- Klehmann-Hieb, E -- De Plaen, E -- Hankeln, T -- Meyer zum Buschenfelde, K H -- Beach, D -- New York, N.Y. -- Science. 1995 Sep 1;269(5228):1281-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universitat, Mainz, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7652577" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Carrier Proteins/metabolism/*pharmacology ; *Cell Cycle Proteins ; Cell Line ; Cloning, Molecular ; Cyclin-Dependent Kinase 4 ; Cyclin-Dependent Kinase Inhibitor p15 ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p27 ; *Cyclin-Dependent Kinases ; Cyclins/metabolism/pharmacology ; HLA-A2 Antigen/immunology ; Humans ; Melanoma/enzymology/*immunology ; Microtubule-Associated Proteins/metabolism/pharmacology ; Molecular Sequence Data ; Point Mutation ; Polymerase Chain Reaction ; Protein-Serine-Threonine Kinases/antagonists & ; inhibitors/genetics/*immunology/metabolism ; *Proto-Oncogene Proteins ; T-Lymphocytes, Cytotoxic/*immunology ; Transfection ; Tumor Cells, Cultured ; *Tumor Suppressor Proteins
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  • 31
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weissman, J S -- Sigler, P B -- Horwich, A L -- New York, N.Y. -- Science. 1995 Apr 28;268(5210):523-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7725096" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Archaeal Proteins ; Binding Sites ; Chaperonin 60/*chemistry/metabolism ; Cysteine Endopeptidases/*chemistry/metabolism ; Endopeptidases ; Multienzyme Complexes/*chemistry/metabolism ; Proteasome Endopeptidase Complex ; Protein Folding ; Proteins/*metabolism ; Thermoplasma/enzymology ; Ubiquitins/metabolism
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  • 32
    Publication Date: 1995-07-21
    Description: Huntington's disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function. To distinguish between "loss of function" and "gain of function" models of HD, the murine HD homolog Hdh was inactivated by gene targeting. Mice heterozygous for Hdh inactivation were phenotypically normal, whereas homozygosity resulted in embryonic death. Homozygotes displayed abnormal gastrulation at embryonic day 7.5 and were resorbing by day 8.5. Thus, huntingtin is critical early in embryonic development, before the emergence of the nervous system. That Hdh inactivation does not mimic adult HD neuropathology suggests that the human disease involves a gain of function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duyao, M P -- Auerbach, A B -- Ryan, A -- Persichetti, F -- Barnes, G T -- McNeil, S M -- Ge, P -- Vonsattel, J P -- Gusella, J F -- Joyner, A L -- NS16367/NS/NINDS NIH HHS/ -- NS32765/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1995 Jul 21;269(5222):407-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7618107" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Ectoderm/cytology ; Embryonic and Fetal Development ; Female ; Gene Targeting ; Genotype ; Heterozygote ; Homozygote ; Humans ; Huntington Disease/*genetics ; Male ; Mesoderm/cytology ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Nerve Tissue Proteins/*genetics/physiology ; Nuclear Proteins/*genetics/physiology ; Phenotype ; Stem Cells/metabolism
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  • 33
    Publication Date: 1995-11-10
    Description: Polychlorinated biphenyls (PCBs) typify a class of stable aromatic pollutants that are targeted by bioremediation strategies. In the aerobic degradation of biphenyl by bacteria, the key step of ring cleavage is catalyzed by an Fe(II)-dependent extradiol dioxygenase. The crystal structure of 2,3-dihydroxybiphenyl 1,2-dioxygenase from a PCB-degrading strain of Pseudomonas cepacia has been determined at 1.9 angstrom resolution. The monomer comprises amino- and carboxyl-terminal domains. Structural homology between and within the domains reveals evolutionary relationships within the extradiol dioxygenase family. The iron atom has five ligands in square pyramidal geometry: one glutamate and two histidine side chains, and two water molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, S -- Eltis, L D -- Timmis, K N -- Muchmore, S W -- Bolin, J T -- GM 52831/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Nov 10;270(5238):976-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-1392, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481800" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Biodegradation, Environmental ; Crystallography, X-Ray ; *Dioxygenases ; Evolution, Molecular ; Ferrous Compounds/chemistry/metabolism ; Hydrogen Bonding ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Oxygen/chemistry/metabolism ; Oxygenases/*chemistry/metabolism ; Polychlorinated Biphenyls/metabolism ; *Protein Conformation ; Protein Structure, Secondary ; Pseudomonas/*enzymology ; Sequence Alignment
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-08-04
    Description: Eukaryotic DNA polymerase beta (pol beta) can catalyze DNA synthesis during base excision DNA repair. It is shown here that pol beta also catalyzes release of 5'-terminal deoxyribose phosphate (dRP) residues from incised apurinic-apyrimidinic sites, which are common intermediate products in base excision repair. The catalytic domain for this activity resides within an amino-terminal 8-kilodalton fragment of pol beta, which comprises a distinct structural domain of the enzyme. Magnesium is required for the release of dRP from double-stranded DNA but not from a single-stranded oligonucleotide. Analysis of the released products indicates that the excision reaction occurs by beta-elimination rather than hydrolysis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsumoto, Y -- Kim, K -- CA06927/CA/NCI NIH HHS/ -- CA63154/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1995 Aug 4;269(5224):699-702.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7624801" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apurinic Acid ; Base Sequence ; Binding Sites ; DNA/*metabolism ; DNA Ligases/metabolism ; DNA Polymerase I/*metabolism ; *DNA Repair ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; Deoxyribonuclease IV (Phage T4-Induced) ; Edetic Acid/pharmacology ; Hydrolysis ; Lyases/metabolism ; Molecular Sequence Data ; Polynucleotides ; Protein Structure, Tertiary ; Rats ; Ribosemonophosphates/*metabolism ; Xenopus laevis
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  • 35
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-01-06
    Description: Computer modeling suggested that transcription factors with novel sequence specificities could be designed by combining known DNA binding domains. This structure-based strategy was tested by construction of a fusion protein, ZFHD1, that contained zinc fingers 1 and 2 from Zif268, a short polypeptide linker, and the homeodomain from Oct-1. The fusion protein bound optimally to a sequence containing adjacent homeodomain (TAATTA) and zinc finger (NGGGNG) subsites. When fused to an activation domain, ZFHD1 regulated promoter activity in vivo in a sequence-specific manner. Analysis of known protein-DNA complexes suggests that many other DNA binding proteins could be designed in a similar fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pomerantz, J L -- Sharp, P A -- Pabo, C O -- P01-CA42063/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1995 Jan 6;267(5194):93-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7809612" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Cloning, Molecular ; Computer Simulation ; DNA-Binding Proteins/*chemistry/genetics/metabolism ; Gene Expression Regulation ; Homeodomain Proteins/chemistry ; Host Cell Factor C1 ; Models, Molecular ; Molecular Sequence Data ; Octamer Transcription Factor-1 ; Promoter Regions, Genetic ; Protein Engineering ; Recombinant Fusion Proteins/*chemistry/metabolism ; Transcription Factors/*chemistry/genetics/metabolism ; Transfection ; *Zinc Fingers
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  • 36
    Publication Date: 1995-08-04
    Description: Combinations of antiretroviral drugs that prevent or delay the appearance of drug-resistant human immunodeficiency virus-type 1 (HIV-1) mutants are urgently required. Mutants resistant to 3'-azidothymidine (AZT, zidovudine) became phenotypically sensitive in vitro by mutation of residue 184 of viral reverse transcriptase to valine, which also induced resistance to (-)2'-deoxy-3'-thiacytidine (3TC). Furthermore, AZT-3TC coresistance was not observed during extensive in vitro selection with both drugs. In vivo AZT-3TC combination therapy resulted in a markedly greater decreased in serum HIV-1 RNA concentrations than treatment with AZT alone, even though valine-184 mutants rapidly emerged. Most samples assessed from the combination group remained AZT sensitive at 24 weeks of therapy, consistent with in vitro mutation studies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larder, B A -- Kemp, S D -- Harrigan, P R -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1995 Aug 4;269(5224):696-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Antiviral Therapeutic Research Unit, Wellcome Research Laboratories, Beckenham, Kent, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7542804" target="_blank"〉PubMed〈/a〉
    Keywords: Antiviral Agents/*pharmacology/therapeutic use ; Base Sequence ; CD4 Lymphocyte Count ; Cell Line ; Codon ; Drug Resistance, Microbial ; Drug Therapy, Combination ; HIV Infections/*drug therapy/virology ; HIV Reverse Transcriptase ; HIV-1/*drug effects/enzymology/genetics/growth & development ; HeLa Cells ; Humans ; Lamivudine ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Point Mutation ; RNA, Viral/blood ; RNA-Directed DNA Polymerase/genetics ; *Reverse Transcriptase Inhibitors ; Serial Passage ; Zalcitabine/*analogs & derivatives/pharmacology/therapeutic use ; Zidovudine/*pharmacology/therapeutic use
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  • 37
    Publication Date: 1995-03-24
    Description: Gap junctions are made up of connexin proteins, which comprise a multigene family in mammals. Targeted mutagenesis of connexin43 (Cx43), one of the most prevalent connexin proteins, showed that its absence was compatible with survival of mouse embryos to term, even though mutant cell lines showed reduced dye coupling in vitro. However, mutant embryos died at birth, as a result of a failure in pulmonary gas exchange caused by a swelling and blockage of the right ventricular outflow tract from the heart. This finding suggests that Cx43 plays an essential role in heart development but that there is functional compensation among connexins in other parts of the developing fetus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reaume, A G -- de Sousa, P A -- Kulkarni, S -- Langille, B L -- Zhu, D -- Davies, T C -- Juneja, S C -- Kidder, G M -- Rossant, J -- New York, N.Y. -- Science. 1995 Mar 24;267(5205):1831-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7892609" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Connexin 43/*genetics/*physiology ; Embryo, Mammalian/cytology ; Heart Defects, Congenital/*genetics/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Respiratory Transport/genetics ; Stem Cells ; Ventricular Outflow Obstruction/congenital/genetics
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  • 38
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-11-17
    Description: Cadherins mediate cell adhesion and are essential for normal development. Embryonic stem cells were transfected with a dominant negative N-cadherin mutant (NCAD delta) under the control of promoters active in small intestinal epithelial cells and then introduced into C57BL/6 mouse blastocysts. Analysis of adult chimeric mice revealed that expression of NCAD delta along the entire crypt-villus axis, but not in the villus epithelium alone, produced an inflammatory bowel disease resembling Crohn's disease. NCAD delta perturbed proliferation, migration, and death programs in crypts, which lead to adenomas. This model provides insights about cadherin function in an adult organ and the factors underlying inflammatory bowel disease and intestinal neoplasia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hermiston, M L -- Gordon, J I -- DK30292/DK/NIDDK NIH HHS/ -- DK39760/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1995 Nov 17;270(5239):1203-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7502046" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoma/*etiology/metabolism/pathology ; Animals ; Apoptosis ; Cadherins/biosynthesis/genetics/*physiology ; Cell Division ; Cell Line ; Cell Movement ; Chimera ; Crohn Disease/etiology/immunology/metabolism/pathology ; Immunity, Mucosal ; Inflammatory Bowel Diseases/*etiology/immunology/metabolism/pathology ; Intestinal Mucosa/immunology/metabolism/*pathology ; Intestinal Neoplasms/*etiology/metabolism/pathology ; Intestine, Small/pathology ; Jejunum/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation ; Stem Cells ; Transfection
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  • 39
    Publication Date: 1995-09-01
    Description: The adhesion domain of human CD2 bears a single N-linked carbohydrate. The solution structure of a fragment of CD2 containing the covalently bound high-mannose N-glycan [-(N-acetylglucosamine)2-(mannose)5-8] was solved by nuclear magnetic resonance. The stem and two of three branches of the carbohydrate structure are well defined and the mobility of proximal glycan residues is restricted. Mutagenesis of all residues in the vicinity of the glycan suggests that the glycan is not a component of the CD2-CD58 interface; rather, the carbohydrate stabilizes the protein fold by counterbalancing an unfavorable clustering of five positive charges centered about lysine-61 of CD2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wyss, D F -- Choi, J S -- Li, J -- Knoppers, M H -- Willis, K J -- Arulanandam, A R -- Smolyar, A -- Reinherz, E L -- Wagner, G -- New York, N.Y. -- Science. 1995 Sep 1;269(5228):1273-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7544493" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylglucosamine/chemistry ; Amino Acid Sequence ; Animals ; Antigens, CD/metabolism ; Antigens, CD2/*chemistry/metabolism ; Antigens, CD58 ; Binding Sites ; CHO Cells ; Carbohydrate Conformation ; Carbohydrate Sequence ; Cell Adhesion ; Cricetinae ; Glycosylation ; Humans ; Magnetic Resonance Spectroscopy ; Membrane Glycoproteins/metabolism ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligosaccharides/*chemistry ; *Protein Conformation
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  • 40
    Publication Date: 1995-12-22
    Description: The mitogen-activated protein kinase (MAPK) pathway is a conserved eukaryotic signaling module that converts receptor signals into various outputs. MAPK is activated through phosphorylation by MAPK kinase (MAPKK), which is first activated by MAPKK kinase (MAPKKK). A genetic selection based on a MAPK pathway in yeast was used to identify a mouse protein kinase (TAK1) distinct from other members of the MAPKKK family. TAK1 was shown to participate in regulation of transcription by transforming growth factor-beta (TGF-beta). Furthermore, kinase activity of TAK1 was stimulated in response to TGF-beta and bone morphogenetic protein. These results suggest that TAK1 functions as a mediator in the signaling pathway of TGF-beta superfamily members.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamaguchi, K -- Shirakabe, K -- Shibuya, H -- Irie, K -- Oishi, I -- Ueno, N -- Taniguchi, T -- Nishida, E -- Matsumoto, K -- New York, N.Y. -- Science. 1995 Dec 22;270(5244):2008-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Faculty of Science, Nagoya University, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8533096" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Bone Morphogenetic Proteins ; Cell Line ; Cloning, Molecular ; Epidermal Growth Factor/pharmacology ; *Gene Expression Regulation ; Genes, Reporter ; *MAP Kinase Kinase Kinases ; Mice ; Molecular Sequence Data ; Protein-Serine-Threonine Kinases/*metabolism ; Proteins/pharmacology ; Saccharomyces cerevisiae/genetics ; *Signal Transduction ; Transfection ; Transforming Growth Factor beta/*pharmacology
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  • 41
    Publication Date: 1995-11-17
    Description: Strategies for the treatment of human immunodeficiency virus-type 1 (HIV-1) infection must contend with the obstacle of drug resistance. HIV-1 nucleocapsid protein zinc fingers are prime antiviral targets because they are mutationally intolerant and are required both for acute infection and virion assembly. Nontoxic disulfide-substituted benzamides were identified that attack the zinc fingers, inactivate cell-free virions, inhibit acute and chronic infections, and exhibit broad antiretroviral activity. The compounds were highly synergistic with other antiviral agents, and resistant mutants have not been detected. Zinc finger-reactive compounds may offer an anti-HIV strategy that restricts drug-resistance development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice, W G -- Supko, J G -- Malspeis, L -- Buckheit, R W Jr -- Clanton, D -- Bu, M -- Graham, L -- Schaeffer, C A -- Turpin, J A -- Domagala, J -- Gogliotti, R -- Bader, J P -- Halliday, S M -- Coren, L -- Sowder, R C 2nd -- Arthur, L O -- Henderson, L E -- New York, N.Y. -- Science. 1995 Nov 17;270(5239):1194-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Antiviral Drug Mechanisms, PRI/DynCorp., National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7502043" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antiviral Agents/chemistry/pharmacokinetics/*pharmacology ; Benzamides/chemistry/pharmacokinetics/*pharmacology ; Biological Availability ; Capsid/chemistry/*metabolism ; *Capsid Proteins ; Cell Line ; Disulfides/chemistry/pharmacokinetics/*pharmacology ; Drug Resistance, Microbial ; Drug Synergism ; Gene Products, gag/*antagonists & inhibitors/chemistry ; HIV-1/*drug effects/physiology ; Humans ; Male ; Mice ; Molecular Sequence Data ; *Viral Proteins ; Zinc Fingers/*drug effects ; gag Gene Products, Human Immunodeficiency Virus
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  • 42
    Publication Date: 1995-08-25
    Description: Vulval induction during Caenorhabditis elegans development is mediated by LET-23, a homolog of the mammalian epidermal growth factor receptor tyrosine kinase. The sli-1 gene is a negative regulator of LET-23 and is shown here to encode a protein similar to c-Cbl, a mammalian proto-oncoprotein. SLI-1 and c-Cbl share approximately 55 percent amino acid identity over a stretch of 390 residues, which includes a C3HC4 zinc-binding motif known as the RING finger, and multiple consensus binding sites for Src homology 3 (SH3) domains. SLI-1 and c-Cbl may define a new class of proteins that modify receptor tyrosine kinase-mediated signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoon, C H -- Lee, J -- Jongeward, G D -- Sternberg, P W -- New York, N.Y. -- Science. 1995 Aug 25;269(5227):1102-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7652556" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Caenorhabditis elegans/*genetics/growth & development ; *Caenorhabditis elegans Proteins ; Conserved Sequence ; DNA, Complementary/genetics ; Female ; *Genes, Helminth ; *Genes, Regulator ; Helminth Proteins/chemistry/*genetics/metabolism ; Humans ; Molecular Sequence Data ; Mutation ; Proto-Oncogene Proteins/chemistry/*genetics ; Proto-Oncogene Proteins c-cbl ; Receptor, Epidermal Growth Factor/metabolism ; Sequence Alignment ; Signal Transduction ; *Ubiquitin-Protein Ligases ; Vulva/growth & development
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  • 43
    Publication Date: 1995-11-10
    Description: Crystallographic analysis of 2.2 angstrom resolution shows that guanosine triphosphate (GTP) hydrolysis triggers conformational changes in the heterotrimeric G-protein alpha subunit, Gi alpha 1. The switch II and switch III segments become disordered, and linker II connecting the Ras and alpha helical domains moves, thus altering the structures of potential effector and beta gamma binding regions. Contacts between the alpha-helical and Ras domains are weakened, possibly facilitating the release of guanosine diphosphate (GDP). The amino and carboxyl termini, which contain receptor and beta gamma binding determinants, are disordered in the complex with GTP, but are organized into a compact microdomain on GDP hydrolysis. The amino terminus also forms extensive quaternary contacts with neighboring alpha subunits in the lattice, suggesting that multimers of alpha subunits or heterotrimers may play a role in signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mixon, M B -- Lee, E -- Coleman, D E -- Berghuis, A M -- Gilman, A G -- Sprang, S R -- DK 46371/DK/NIDDK NIH HHS/ -- GM34497/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Nov 10;270(5238):954-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9050, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481799" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; GTP-Binding Proteins/*chemistry/metabolism ; Guanosine 5'-O-(3-Thiotriphosphate)/metabolism ; Guanosine Diphosphate/*metabolism ; Guanosine Triphosphate/*metabolism ; Hydrogen Bonding ; Hydrolysis ; Magnesium/metabolism ; Models, Molecular ; *Protein Conformation ; Protein Structure, Secondary ; *Protein Structure, Tertiary
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  • 44
    Publication Date: 1995-06-09
    Description: Fluorescent probes offer insight into the highly localized and rapid molecular events that underlie cell function. However, methods are required that can efficiently transform the limited signals from such probes into high-resolution images. An algorithm has now been developed that produces highly accurate images of fluorescent probe distribution inside cells with minimal light exposure and a conventional light microscope. This method provides resolution nearly four times greater than that currently available from any fluorescence microscope and was used to study several biological problems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carrington, W A -- Lynch, R M -- Moore, E D -- Isenberg, G -- Fogarty, K E -- Fay, F S -- New York, N.Y. -- Science. 1995 Jun 9;268(5216):1483-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Molecular Medicine, University of Massachusetts Medical School, Worcester 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7770772" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Calcium Channels/analysis ; Cell Line ; Cell Physiological Phenomena ; Cells/*chemistry/*ultrastructure ; Cells, Cultured ; Fluorescence ; *Fluorescent Dyes ; Guinea Pigs ; Hexokinase/analysis ; *Image Processing, Computer-Assisted ; Light ; Microscopy, Fluorescence ; Microtubules/ultrastructure ; Muscle Proteins/analysis ; Muscle, Smooth/cytology/enzymology ; Rats ; Ryanodine Receptor Calcium Release Channel
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  • 45
    Publication Date: 1995-04-21
    Description: Sulfonylureas are a class of drugs widely used to promote insulin secretion in the treatment of non-insulin-dependent diabetes mellitus. These drugs interact with the sulfonylurea receptor of pancreatic beta cells and inhibit the conductance of adenosine triphosphate (ATP)-dependent potassium (KATP) channels. Cloning of complementary DNAs for the high-affinity sulfonylurea receptor indicates that it is a member of the ATP-binding cassette or traffic ATPase superfamily with multiple membrane-spanning domains and two nucleotide binding folds. The results suggest that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect KATP channel activity, and thereby modulate insulin release.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aguilar-Bryan, L -- Nichols, C G -- Wechsler, S W -- Clement, J P 4th -- Boyd, A E 3rd -- Gonzalez, G -- Herrera-Sosa, H -- Nguy, K -- Bryan, J -- Nelson, D A -- DK41898/DK/NIDDK NIH HHS/ -- DK44311/DK/NIDDK NIH HHS/ -- HL45742/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1995 Apr 21;268(5209):423-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7716547" target="_blank"〉PubMed〈/a〉
    Keywords: *ATP-Binding Cassette Transporters ; Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Cloning, Molecular ; Cricetinae ; Insulin/*secretion ; Islets of Langerhans/*metabolism ; Molecular Sequence Data ; Phosphorylation ; Potassium Channels/chemistry/*genetics/metabolism ; *Potassium Channels, Inwardly Rectifying ; Protein Folding ; Protein Structure, Secondary ; Receptors, Drug/chemistry/*genetics/metabolism ; Sequence Alignment ; Sulfonylurea Compounds/metabolism ; Sulfonylurea Receptors ; Transfection ; Tumor Cells, Cultured
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  • 46
    Publication Date: 1995-04-14
    Description: One Ras-dependent protein kinase cascade leading from growth factor receptors to the ERK (extracellular signal-regulated kinases) subgroup of mitogen-activated protein kinases (MAPKs) is dependent on the protein kinase Raf-1, which activates the MEK (MAPK or ERK kinase) dual specificity kinases. A second protein kinase cascade leading to activation of the Jun kinases (JNKs) is dependent on MEKK (MEK kinase). A dual-specificity kinase that activates JNK, named JNKK, was identified that functions between MEKK and JNK. JNKK activated the JNKs but did not activate the ERKs and was unresponsive to Raf-1 in transfected HeLa cells. JNKK also activated another MAPK, p38 (Mpk2; the mammalian homolog of HOG1 from yeast), whose activity is regulated similarly to that of the JNKs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, A -- Minden, A -- Martinetto, H -- Claret, F X -- Lange-Carter, C -- Mercurio, F -- Johnson, G L -- Karin, M -- New York, N.Y. -- Science. 1995 Apr 14;268(5208):286-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of California-San Diego School of Medicine, La Jolla 92093-0636, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7716521" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Cell Line ; Enzyme Activation ; Epidermal Growth Factor/pharmacology ; HeLa Cells ; Humans ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Kinase 4 ; *MAP Kinase Kinase Kinase 1 ; *Mitogen-Activated Protein Kinase Kinases ; *Mitogen-Activated Protein Kinases ; Molecular Sequence Data ; Phosphorylation ; Protein Kinases/chemistry/*metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-raf ; Recombinant Fusion Proteins/metabolism ; Substrate Specificity ; Transfection ; p38 Mitogen-Activated Protein Kinases
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  • 47
    Publication Date: 1995-12-08
    Description: A stepwise approach for reducing the size of a polypeptide hormone, atrial natriuretic peptide (ANP), from 28 residues to 15 while retaining high biopotency is described. Systematic structural and functional analysis identified a discontinuous functional epitope for receptor binding and activation, most of which was placed onto a smaller ring (Cys6 to Cys17) that was created by repositioning the ANP native disulfide bond (Cys7 to Cys23). High affinity was subsequently restored by optimizing the remaining noncritical residues by means of phage display. Residues that flanked the mini-ring structure were then deleted in stages, and affinity losses were rectified by additional phage-sorting experiments. Thus, structural and functional data on hormones, coupled with phage display methods, can be used to shrink the hormones to moieties more amendable to small-molecule design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, B -- Tom, J Y -- Oare, D -- Yen, R -- Fairbrother, W J -- Wells, J A -- Cunningham, B C -- New York, N.Y. -- Science. 1995 Dec 8;270(5242):1657-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Engineering, Genenteeh, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7502074" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Atrial Natriuretic Factor/*chemistry/genetics/immunology/metabolism ; Base Sequence ; Cell Line ; Cyclic GMP/metabolism ; Epitopes ; Guanylate Cyclase/metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Protein Conformation ; *Protein Engineering ; Receptors, Atrial Natriuretic Factor/metabolism
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  • 48
    Publication Date: 1995-02-24
    Description: Mandelate racemase and muconate lactonizing enzyme are structurally homologous but catalyze different reactions, each initiated by proton abstraction from carbon. The structural similarity to mandelate racemase of a previously unidentified gene product was used to deduce its function as a galactonate dehydratase. In this enzyme superfamily that has evolved to catalyze proton abstraction from carbon, three variations of homologous active site architectures are now represented: lysine and histidine bases in the active site of mandelate racemase, only a lysine base in the active site of muconate lactonizing enzyme, and only a histidine base in the active site of galactonate dehydratase. This discovery supports the hypothesis that new enzymatic activities evolve by recruitment of a protein catalyzing the same type of chemical reaction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Babbitt, P C -- Mrachko, G T -- Hasson, M S -- Huisman, G W -- Kolter, R -- Ringe, D -- Petsko, G A -- Kenyon, G L -- Gerlt, J A -- GM-34572/GM/NIGMS NIH HHS/ -- GM-40570/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Feb 24;267(5201):1159-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7855594" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Histidine/metabolism ; Hydro-Lyases/chemistry/genetics/*metabolism ; *Intramolecular Lyases ; Isomerases/chemistry/*metabolism ; Lysine/metabolism ; Molecular Sequence Data ; Open Reading Frames ; Operon ; *Protons ; Pseudomonas putida/*enzymology/genetics ; Racemases and Epimerases/chemistry/*metabolism
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  • 49
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-04-21
    Description: Fas is a cell surface receptor that controls a poorly understood signal transduction pathway that leads to cell death by means of apoptosis. A protein tyrosine phosphatase, FAP-1, capable of interacting with the cytosolic domain of Fas, was identified. The carboxyl terminal 15 amino acids of Fas are necessary and sufficient for interaction with FAP-1. FAP-1 expression is highest in tissues and cell lines that are relatively resistant to Fas-mediated cytotoxicity. Gene transfer-mediated elevations in FAP-1 partially abolished Fas-induced apoptosis in a T cell line. These findings are consistent with an inhibitory effect of FAP-1 on Fas signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sato, T -- Irie, S -- Kitada, S -- Reed, J C -- New York, N.Y. -- Science. 1995 Apr 21;268(5209):411-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉La Jolla Cancer Research Foundation, Oncogene and Tumor Suppressor Gene Program, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7536343" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, CD95 ; Antigens, Surface/genetics/*metabolism ; Apoptosis ; Base Sequence ; Cell Line ; Cloning, Molecular ; DNA, Complementary/genetics ; Humans ; Mice ; Molecular Sequence Data ; Protein Tyrosine Phosphatases/genetics/*metabolism ; Receptors, Cell Surface/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; T-Lymphocytes/cytology
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  • 50
    Publication Date: 1995-01-06
    Description: Specificity of protein kinases and phosphatases may be achieved through compartmentalization with preferred substrates. In neurons, adenosine 3', 5'-monophosphate (cAMP)-dependent protein kinase (PKA) is localized at postsynaptic densities by association of its regulatory subunit with an A kinase anchor protein, AKAP79. Interaction cloning experiments demonstrated that AKAP79 also binds protein phosphatase 2B, or calcineurin (CaN). A ternary complex of PKA, AKAP, and CaN was isolated from bovine brain, and colocalization of the kinase and the phosphatase was established in neurites of cultured hippocampal neurons. The putative CaN-binding domain of AKAP79 is similar to that of the immunophilin FKBP-12, and AKAP79 inhibited CaN phosphatase activity. These results suggest that both PKA and CaN are targeted to subcellular sites by association with a common anchor protein and thereby regulate the phosphorylation state of key neuronal substrates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coghlan, V M -- Perrino, B A -- Howard, M -- Langeberg, L K -- Hicks, J B -- Gallatin, W M -- Scott, J D -- DK09059/DK/NIDDK NIH HHS/ -- GM48231/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Jan 6;267(5194):108-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health Sciences University, Portland 97201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7528941" target="_blank"〉PubMed〈/a〉
    Keywords: A Kinase Anchor Proteins ; *Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; Binding Sites ; *Brain Chemistry ; Calcineurin ; Calmodulin-Binding Proteins/analysis/antagonists & inhibitors/*metabolism ; Carrier Proteins/analysis ; Cattle ; Cells, Cultured ; Cyclic AMP-Dependent Protein Kinases/analysis/*metabolism ; Hippocampus/chemistry ; Molecular Sequence Data ; Neurites/chemistry ; Phosphoprotein Phosphatases/analysis/antagonists & inhibitors/*metabolism ; Phosphorylation ; Proteins/*metabolism/pharmacology ; Rats ; Recombinant Proteins/pharmacology ; Tacrolimus/pharmacology
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  • 51
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-05-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lippard, S J -- New York, N.Y. -- Science. 1995 May 19;268(5213):996-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7754394" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallization ; Crystallography, X-Ray ; Models, Molecular ; Urease/*chemistry/metabolism
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  • 52
    Publication Date: 1995-10-13
    Description: Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents. They inhibit synthesis of almost all known cytokines and of several cell surface molecules required for immune function, but the mechanism underlying this activity has been unclear. Here it is shown that glucocorticoids are potent inhibitors of nuclear factor kappa B (NF-kappa B) activation in mice and cultured cells. This inhibition is mediated by induction of the I kappa B alpha inhibitory protein, which traps activated NF-kappa B in inactive cytoplasmic complexes. Because NF-kappa B activates many immunoregulatory genes in response to pro-inflammatory stimuli, the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Auphan, N -- DiDonato, J A -- Rosette, C -- Helmberg, A -- Karin, M -- New York, N.Y. -- Science. 1995 Oct 13;270(5234):286-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569976" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Inflammatory Agents/*pharmacology ; Cell Line ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; DNA-Binding Proteins/*biosynthesis ; Dexamethasone/*pharmacology ; Humans ; Hybridomas ; *I-kappa B Proteins ; *Immunosuppression ; Interleukin-2/pharmacology ; Lymph Nodes/drug effects/metabolism ; Mice ; NF-kappa B/*antagonists & inhibitors/metabolism ; Receptors, Glucocorticoid/metabolism ; T-Lymphocytes/drug effects/*metabolism ; Tetradecanoylphorbol Acetate/pharmacology ; Transcription Factor AP-1/metabolism ; Transcription Factor RelA ; Tumor Cells, Cultured
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  • 53
    Publication Date: 1995-08-04
    Description: The crystal structure of restriction endonuclease Bam HI complexed to DNA has been determined at 2.2 angstrom resolution. The DNA binds in the cleft and retains a B-DNA type of conformation. The enzyme, however, undergoes a series of conformational changes, including rotation of subunits and folding of disordered regions. The most striking conformational change is the unraveling of carboxyl-terminal alpha helices to form partially disordered "arms." The arm from one subunit fits into the minor groove while the arm from the symmetry related subunit follows the DNA sugar-phosphate backbone. Recognition of DNA base pairs occurs primarily in the major groove, with a few interactions occurring in the minor groove. Tightly bound water molecules play an equally important role as side chain and main chain atoms in the recognition of base pairs. The complex also provides new insights into the mechanism by which the enzyme catalyzes the hydrolysis of DNA phosphodiester groups.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newman, M -- Strzelecka, T -- Dorner, L F -- Schildkraut, I -- Aggarwal, A K -- GM-44006/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Aug 4;269(5224):656-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7624794" target="_blank"〉PubMed〈/a〉
    Keywords: Base Composition ; Base Sequence ; Binding Sites ; Catalysis ; Computer Graphics ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; Deoxyribonuclease BamHI/*chemistry/*metabolism ; Deoxyribonuclease EcoRI/chemistry ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Protein Conformation ; *Protein Folding ; Protein Structure, Secondary
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  • 54
    Publication Date: 1995-10-13
    Description: Glucocorticoids are potent immunosuppressive drugs, but their mechanism is poorly understood. Nuclear factor kappa B (NF-kappa B), a regulator of immune system and inflammation genes, may be a target for glucocorticoid-mediated immunosuppression. The activation of NF-kappa B involves the targeted degradation of its cytoplasmic inhibitor, I kappa B alpha, and the translocation of NF-kappa B to the nucleus. Here it is shown that the synthetic glucocorticoid dexamethasone induces the transcription of the I kappa B alpha gene, which results in an increased rate of I kappa B alpha protein synthesis. Stimulation by tumor necrosis factor causes the release of NF-kappa B from I kappa B alpha. However, in the presence of dexamethasone this newly released NF-kappa B quickly reassociates with newly synthesized I kappa B alpha, thus markedly reducing the amount of NF-kappa B that translocates to the nucleus. This decrease in nuclear NF-kappa B is predicted to markedly decrease cytokine secretion and thus effectively block the activation of the immune system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheinman, R I -- Cogswell, P C -- Lofquist, A K -- Baldwin, A S Jr -- AI35098/AI/NIAID NIH HHS/ -- CA52515/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1995 Oct 13;270(5234):283-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569975" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cell Nucleus/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Dexamethasone/*pharmacology ; HeLa Cells ; Humans ; *I-kappa B Proteins ; *Immunosuppression ; Immunosuppressive Agents/*pharmacology ; Lipopolysaccharides/pharmacology ; NF-kappa B/genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; Signal Transduction/drug effects ; Transcription Factor RelA ; Transcription, Genetic/drug effects ; Tumor Necrosis Factor-alpha/pharmacology
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  • 55
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-12-15
    Description: Coordinate activation of transcription by multiple enhancer binding factors is essential for the regulation of pattern formation during development of Drosophila melanogaster. Cell-free transcription reactions are described that recapitulate transcriptional synergism directed by the Drosophila developmental regulators Bicoid (BCD) and Hunchback (HB). Within the basal transcription factor complex TFIID, two specific targets, TAFII110 and TAFII60, served as coactivators to mediate transcriptional activation by these two enhancer binding proteins. A quadruple complex containing TATA binding protein (TBP), TAFII250, TAFII110, and TAFII60 mediated transcriptional synergism by BCD and HB, whereas triple TBP-TAFII complexes lacking one or the other target coactivator failed to support synergistic activation. Deoxyribonuclease I footprint protection experiments revealed that an integral step leading to transcriptional synergism involves the recruitment of TBP-TAFII complexes to the promoter by way of multivalent contacts between activators and selected TAFIIs. Thus, the concerted action of multiple regulators with different coactivators helps to establish the pattern and level of segmentation gene transcription during Drosophila development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sauer, F -- Hansen, S K -- Tjian, R -- New York, N.Y. -- Science. 1995 Dec 15;270(5243):1783-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8525367" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; DNA-Binding Proteins/metabolism ; *Drosophila Proteins ; Drosophila melanogaster/embryology/genetics ; Enhancer Elements, Genetic ; *Gene Expression Regulation, Developmental ; *Homeodomain Proteins ; Insect Hormones/*genetics ; Juvenile Hormones/*genetics ; Protein Binding ; Recombinant Proteins ; TATA Box ; TATA-Box Binding Protein ; *Trans-Activators ; Transcription Factor TFIID ; Transcription Factors/*metabolism ; *Transcriptional Activation
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 56
    Publication Date: 1995-12-08
    Description: Pineal serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, or AA-NAT) generates the large circadian rhythm in melatonin, the hormone that coordinates daily and seasonal physiology in some mammals. Complementary DNA encoding ovine AA-NAT was cloned. The abundance of AA-NAT messenger RNA (mRNA) during the day was high in the ovine pineal gland and somewhat lower in retina. AA-NAT mRNA was found unexpectedly in the pituitary gland and in some brain regions. The night-to-day ratio of ovine pineal AA-NAT mRNA is less than 2. In contrast, the ratio exceeds 150 in rats. AA-NAT represents a family within a large superfamily of acetyltransferases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coon, S L -- Roseboom, P H -- Baler, R -- Weller, J L -- Namboodiri, M A -- Koonin, E V -- Klein, D C -- New York, N.Y. -- Science. 1995 Dec 8;270(5242):1681-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section on Neuroendocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7502081" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Arylamine N-Acetyltransferase/*genetics/metabolism ; Brain/metabolism ; Cell Line ; Circadian Rhythm ; *Cloning, Molecular ; DNA, Complementary/genetics ; Molecular Sequence Data ; Pineal Gland/*enzymology/metabolism ; Pituitary Gland/metabolism ; RNA, Messenger/genetics/metabolism ; Rats ; Retina/metabolism ; Sequence Alignment ; Sheep ; Transfection
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 57
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kazantsev, A -- Sancar, A -- 32833/PHS HHS/ -- New York, N.Y. -- Science. 1995 Nov 10;270(5238):1003-4; author reply 1005-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481776" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cell-Free System ; DNA Damage ; *DNA Repair ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins ; Proliferating Cell Nuclear Antigen/metabolism ; Proteins/metabolism/*pharmacology
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  • 58
    Publication Date: 1995-01-20
    Description: Cadherins are calcium-dependent cell adhesion molecules containing extracellular repeats of approximately 110 amino acids. The three-dimensional structure of the amino-terminal repeat of mouse epithelial cadherin was determined by multidimensional heteronuclear magnetic resonance spectroscopy. The calcium ion was bound by a short alpha helix and by loops at one end of the seven-stranded beta-barrel structure. An exposed concave face is in a position to provide homophilic binding specificity and was also sensitive to calcium ligation. Unexpected structural similarities with the immunoglobulin fold suggest an evolutionary relation between calcium-dependent and calcium-independent cell adhesion molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Overduin, M -- Harvey, T S -- Bagby, S -- Tong, K I -- Yau, P -- Takeichi, M -- Ikura, M -- New York, N.Y. -- Science. 1995 Jan 20;267(5196):386-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular and Structural Biology, Ontario Cancer Institute, Toronto, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7824937" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, CD2/chemistry ; Binding Sites ; Cadherins/*chemistry/metabolism/physiology ; Calcium/*metabolism ; *Cell Adhesion ; Hydrogen Bonding ; Immunoglobulins/chemistry ; Mice ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 59
    Publication Date: 1995-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kearsey, J M -- Shivji, M K -- Hall, P A -- Wood, R D -- New York, N.Y. -- Science. 1995 Nov 10;270(5238):1004-5; author reply 1005-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481777" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; DNA Damage ; DNA Repair/*drug effects ; Genes, p53 ; Humans ; Intracellular Signaling Peptides and Proteins ; Proliferating Cell Nuclear Antigen/metabolism ; Proteins/metabolism/*pharmacology ; Recombinant Fusion Proteins/pharmacology
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  • 60
    Publication Date: 1995-02-17
    Description: Terminal differentiation is coupled to withdrawal from the cell cycle. The cyclin-dependent kinase inhibitor (CKI) p21Cip1 is transcriptionally regulated by p53 and can induce growth arrest. CKIs are therefore potential mediators of developmental control of cell proliferation. The expression pattern of mouse p21 correlated with terminal differentiation of multiple cell lineages including skeletal muscle, cartilage, skin, and nasal epithelium in a p53-independent manner. Although the muscle-specific transcription factor MyoD is sufficient to activate p21 expression in 10T1/2 cells, p21 was expressed in myogenic cells of mice lacking the genes encoding MyoD and myogenin, demonstrating that p21 expression does not require these transcription factors. The p21 protein may function during development as an inducible growth inhibitor that contributes to cell cycle exit and differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parker, S B -- Eichele, G -- Zhang, P -- Rawls, A -- Sands, A T -- Bradley, A -- Olson, E N -- Harper, J W -- Elledge, S J -- AG-11085/AG/NIA NIH HHS/ -- AR39849/AR/NIAMS NIH HHS/ -- AR40339/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Feb 17;267(5200):1024-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, 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/7863329" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle ; *Cell Differentiation ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/*biosynthesis/genetics ; Embryo, Mammalian/metabolism ; *Gene Expression Regulation, Developmental ; In Situ Hybridization ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/*cytology/metabolism ; MyoD Protein/genetics/physiology ; Myogenin/genetics/physiology ; Tumor Suppressor Protein p53/*physiology
    Print ISSN: 0036-8075
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  • 61
    Publication Date: 1995-02-10
    Description: Apoptosis (programmed cell death) plays a major role in development and tissue regeneration. Basement membrane extracellular matrix (ECM), but not fibronectin or collagen, was shown to suppress apoptosis of mammary epithelial cells in tissue culture and in vivo. Apoptosis was induced by antibodies to beta 1 integrins or by overexpression of stromelysin-1, which degrades ECM. Expression of interleukin-1 beta converting enzyme (ICE) correlated with the loss of ECM, and inhibitors of ICE activity prevented apoptosis. These results suggest that ECM regulates apoptosis in mammary epithelial cells through an integrin-dependent negative regulation of ICE expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004777/" 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/PMC3004777/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boudreau, N -- Sympson, C J -- Werb, Z -- Bissell, M J -- CA 57621/CA/NCI NIH HHS/ -- ES 07106/ES/NIEHS NIH HHS/ -- R01 CA057621/CA/NCI NIH HHS/ -- R01 CA057621-07/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1995 Feb 10;267(5199):891-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7531366" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD29 ; *Apoptosis ; Basement Membrane ; Caspase 1 ; Cell Line ; Collagen ; Cysteine Endopeptidases/genetics/*metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; Extracellular Matrix/metabolism/*physiology ; Fibronectins ; Gene Expression Regulation, Enzymologic ; Integrins/immunology ; Mammary Glands, Animal/*cytology/enzymology ; Matrix Metalloproteinase 3 ; Metalloendopeptidases/genetics/metabolism ; Mice ; Mice, Transgenic ; RNA, Messenger/genetics/metabolism ; Transfection
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  • 62
    Publication Date: 1995-02-17
    Description: Skeletal muscle differentiation entails the coordination of muscle-specific gene expression and terminal withdrawal from the cell cycle. This cell cycle arrest in the G0 phase requires the retinoblastoma tumor suppressor protein (Rb). The function of Rb is negatively regulated by cyclin-dependent kinases (Cdks), which are controlled by Cdk inhibitors. Expression of MyoD, a skeletal muscle-specific transcriptional regulator, activated the expression of the Cdk inhibitor p21 during differentiation of murine myocytes and in nonmyogenic cells. MyoD-mediated induction of p21 did not require the tumor suppressor protein p53 and correlated with cell cycle withdrawal. Thus, MyoD may induce terminal cell cycle arrest during skeletal muscle differentiation by increasing the expression of p21.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Halevy, O -- Novitch, B G -- Spicer, D B -- Skapek, S X -- Rhee, J -- Hannon, G J -- Beach, D -- Lassar, A B -- F32ARO8214-01A1/AR/NIAMS NIH HHS/ -- N01-HD-6-2915/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1995 Feb 17;267(5200):1018-21.〈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/7863327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Carrier Proteins ; *Cell Cycle ; *Cell Cycle Proteins ; *Cell Differentiation ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclin-Dependent Kinases/*antagonists & inhibitors ; Cyclins/*biosynthesis/genetics ; *DNA-Binding Proteins ; E2F Transcription Factors ; G0 Phase ; Humans ; Mice ; Microtubule-Associated Proteins/biosynthesis/genetics ; Muscle, Skeletal/*cytology/metabolism ; MyoD Protein/*physiology ; RNA, Messenger/genetics/metabolism ; Retinoblastoma Protein/physiology ; Retinoblastoma-Binding Protein 1 ; Transcription Factor DP1 ; Transcription Factors/metabolism ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/physiology ; *Tumor Suppressor Proteins
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  • 63
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-11-24
    Description: The assembly and transport of major histocompatibility complex (MHC) class II molecules require interaction with the invariant chain. A fragment of the invariant chain, CLIP, occupies the peptide-binding groove of the class II molecule. At endosomal pH, the binding of CLIP to human MHC class II HLA-DR molecules was counteracted by its amino-terminal segment (residues 81 to 89), which facilitated rapid release. The CLIP (81-89) fragment also catalyzed the release of CLIP(90-105) and a subset of other self-peptides, probably by transient interaction with an effector site outside the groove. Thus, CLIP may facilitate peptide loading through an allosteric release mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kropshofer, H -- Vogt, A B -- Stern, L J -- Hammerling, G J -- New York, N.Y. -- Science. 1995 Nov 24;270(5240):1357-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Immunology, German Cancer Research Center, Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481823" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigens, Differentiation, B-Lymphocyte/chemistry/*metabolism ; Binding Sites ; Cell Line ; HLA-DR3 Antigen/*metabolism ; Histocompatibility Antigens Class II/chemistry/*metabolism ; Humans ; Hydrogen-Ion Concentration ; Lysine/chemistry ; Molecular Sequence Data ; Peptide Fragments/metabolism ; Proline/chemistry ; Protein Conformation
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  • 64
    Publication Date: 1995-09-08
    Description: Germline mutations in the von Hippel-Lindau tumor suppressor gene (VHL) predispose individuals to a variety of tumors, including renal carcinoma, hemangioblastoma of the central nervous system, and pheochromocytoma. Here, a cellular transcription factor, Elongin (SIII), is identified as a functional target of the VHL protein. Elongin (SIII) is a heterotrimer consisting of a transcriptionally active subunit (A) and two regulatory subunits (B and C) that activate transcription elongation by RNA polymerase II. The VHL protein was shown to bind tightly and specifically to the Elongin B and C subunits and to inhibit Elongin (SIII) transcriptional activity in vitro. These findings reveal a potentially important transcriptional regulatory network in which the VHL protein may play a key role.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duan, D R -- Pause, A -- Burgess, W H -- Aso, T -- Chen, D Y -- Garrett, K P -- Conaway, R C -- Conaway, J W -- Linehan, W M -- Klausner, R D -- GM41628/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Sep 8;269(5229):1402-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Urologic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7660122" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cloning, Molecular ; Gene Expression Regulation ; *Genes, Tumor Suppressor ; HeLa Cells ; Humans ; *Ligases ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/genetics/*metabolism ; RNA Polymerase II/metabolism ; Recombinant Proteins/metabolism ; Transcription Factors/chemistry/isolation & purification/*metabolism ; *Transcription, Genetic ; *Tumor Suppressor Proteins ; *Ubiquitin-Protein Ligases ; Von Hippel-Lindau Tumor Suppressor Protein ; von Hippel-Lindau Disease/*genetics
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  • 65
    Publication Date: 1995-02-03
    Description: Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Derijard, B -- Raingeaud, J -- Barrett, T -- Wu, I H -- Han, J -- Ulevitch, R J -- Davis, R J -- AI15136/AI/NIAID NIH HHS/ -- CA58396/CA/NCI NIH HHS/ -- GM37696/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Feb 3;267(5198):682-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7839144" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Cell Line ; Cloning, Molecular ; Enzyme Activation ; Humans ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Kinase 3 ; *MAP Kinase Kinase 4 ; Mitogen-Activated Protein Kinase 1 ; *Mitogen-Activated Protein Kinase Kinases ; *Mitogen-Activated Protein Kinases ; Molecular Sequence Data ; Phosphorylation ; Protein-Serine-Threonine Kinases/chemistry/*metabolism ; Protein-Tyrosine Kinases/chemistry/*metabolism ; *Signal Transduction ; Substrate Specificity ; Transfection ; p38 Mitogen-Activated Protein Kinases
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  • 66
    Publication Date: 1995-11-24
    Description: Immune evasion by the human immunodeficiency virus (HIV) is unexplained but may involve the mutation of viral antigens. When cytotoxic T lymphocytes engaged CD4-positive cells that were acutely infected with HIV bearing natural variant epitopes in reverse transcriptase, substantial inhibition of specific antiviral lysis was observed. Mutant viruses capable of these transactive effects could facilitate the persistence of a broad range of HIV variants in the face of an active and specific immune response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meier, U C -- Klenerman, P -- Griffin, P -- James, W -- Koppe, B -- Larder, B -- McMichael, A -- Phillips, R -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1995 Nov 24;270(5240):1360-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, Oxford, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481824" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigenic Variation ; Base Sequence ; CD4-Positive T-Lymphocytes/immunology/virology ; Cell Line ; *Cytotoxicity, Immunologic ; Epitopes/genetics ; HIV Antigens/genetics/*immunology ; HIV Reverse Transcriptase ; HIV-1/enzymology/genetics/*immunology ; HLA-B8 Antigen/immunology ; Humans ; *Immune Tolerance ; Molecular Sequence Data ; RNA-Directed DNA Polymerase/genetics/*immunology ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes, Cytotoxic/*immunology
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  • 67
    Publication Date: 1995-10-13
    Description: Stimulation of rat vascular smooth muscle cells (VSMCs) by platelet-derived growth factor (PDGF) transiently increased the intracellular concentration of hydrogen peroxide (H2O2). This increase could be blunted by increasing the intracellular concentration of the scavenging enzyme catalase or by the chemical antioxidant N-acetylcysteine. The response of VSMCs to PDGF, which includes tyrosine phosphorylation, mitogen-activated protein kinase stimulation, DNA synthesis, and chemotaxis, was inhibited when the growth factor-stimulated rise in H2O2 concentration was blocked. These results suggest that H2O2 may act as a signal-transducing molecule, and they suggest a potential mechanism for the cardioprotective effects of antioxidants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sundaresan, M -- Yu, Z X -- Ferrans, V J -- Irani, K -- Finkel, T -- New York, N.Y. -- Science. 1995 Oct 13;270(5234):296-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiology Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892-1650, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569979" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcysteine/pharmacology ; Adenoviridae/genetics/physiology ; Animals ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Catalase/metabolism ; Cell Line ; Cells, Cultured ; Chemotaxis/drug effects ; Endopeptidase K ; Free Radical Scavengers/pharmacology ; Humans ; Hydrogen Peroxide/*metabolism ; Mitogen-Activated Protein Kinase 1 ; Mitogen-Activated Protein Kinase 3 ; *Mitogen-Activated Protein Kinases ; Muscle, Smooth, Vascular/cytology/drug effects/*metabolism/virology ; Phosphorylation ; Phosphotyrosine/metabolism ; Platelet-Derived Growth Factor/*pharmacology ; Protein-Tyrosine Kinases/metabolism ; Rats ; Serine Endopeptidases/metabolism ; *Signal Transduction
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  • 68
    Publication Date: 1995-08-18
    Description: The Volga German kindreds are a group of seven related families with autosomal dominant early-onset Alzheimer's disease (AD). Linkage to known AD-related loci on chromosomes 21 and 14 has been excluded. Significant evidence for linkage to AD in these families was obtained with D1S479 and there was also positive evidence for linkage with other markers in the region. A 112-base pair allele of D1S479 co-segregated with the disease in five of seven families, which is consistent with a common genetic founder. This study demonstrates the presence of an AD locus on chromosome 1q31-42.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levy-Lahad, E -- Wijsman, E M -- Nemens, E -- Anderson, L -- Goddard, K A -- Weber, J L -- Bird, T D -- Schellenberg, G D -- AG05136/AG/NIA NIH HHS/ -- F32 AG05635/AG/NIA NIH HHS/ -- HG00835/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 1995 Aug 18;269(5226):970-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geriatric Research, Education, and Clinical Center (182B), Veterans Affairs Medical Center, Seattle, WA 98108-1597, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7638621" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Alleles ; Alzheimer Disease/ethnology/*genetics ; Cell Line ; Chromosome Mapping ; Chromosomes, Human, Pair 1/*genetics ; Female ; Genetic Markers ; Genotype ; Germany/ethnology ; Haplotypes ; Humans ; Lod Score ; Male ; Middle Aged ; Pedigree
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  • 69
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-03-24
    Description: Transport of RNAs within nuclei and through nuclear pore complexes (NPCs) are essential, but poorly understood, steps in gene expression. In experiments with mammalian cells, RCC1, the abundant nuclear guanine nucleotide exchange factor for the guanosine triphosphatase Ran/TC4, was shown to be required for nucleocytoplasmic transport of precursors of spliceosomal small nuclear RNAs (snRNAs), intranuclear transport of U3 snRNA, and processing of ribosomal RNAs, but not for export of transfer RNAs. It is proposed that guanosine triphosphate (GTP)-bound Ran/TC4 associates with ribonucleoprotein particles (RNPs) during intranuclear movement, and that GTP hydrolysis promotes deposition of RNPs at targeted sites such as NPCs or nucleoli.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, Y -- Dahlberg, J E -- Lund, E -- GM 30220/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Mar 24;267(5205):1807-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomolecular Chemistry, University of Wisconsin School of Medicine, Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7534442" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Transport/physiology ; *Cell Cycle Proteins ; Cell Line ; Cell Nucleus/*metabolism ; DNA-Binding Proteins/*physiology ; *Guanine Nucleotide Exchange Factors ; Guanosine Triphosphate/metabolism ; Methylation ; Nuclear Proteins/metabolism/*physiology ; RNA/*metabolism ; RNA Precursors/metabolism ; RNA, Ribosomal/metabolism ; RNA, Small Nuclear/metabolism ; RNA, Transfer/metabolism ; Spliceosomes/metabolism ; ran GTP-Binding Protein
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-05-19
    Description: The crystal structure of urease from Klebsiella aerogenes has been determined at 2.2 A resolution and refined to an R factor of 18.2 percent. The enzyme contains four structural domains: three with novel folds playing structural roles, and an (alpha beta)8 barrel domain, which contains the bi-nickel center. The two active site nickels are 3.5 A apart. One nickel ion is coordinated by three ligands (with low occupancy of a fourth ligand) and the second is coordinated by five ligands. A carbamylated lysine provides an oxygen ligand to each nickel, explaining why carbon dioxide is required for the activation of urease apoenzyme. The structure is compatible with a catalytic mechanism whereby urea ligates Ni-1 to complete its tetrahedral coordination and a hydroxide ligand of Ni-2 attacks the carbonyl carbon. A surprisingly high structural similarity between the urease catalytic domain and that of the zinc-dependent adenosine deaminase reveals a remarkable example of active site divergence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jabri, E -- Carr, M B -- Hausinger, R P -- Karplus, P A -- 5T32-GM08384-04/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 May 19;268(5213):998-1004.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7754395" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Biopolymers ; Catalysis ; Crystallography, X-Ray ; Klebsiella pneumoniae/*enzymology ; Models, Molecular ; Mutagenesis, Site-Directed ; Nickel/analysis ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Urease/*chemistry/metabolism
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  • 71
    Publication Date: 1995-12-15
    Description: The template and coactivator requirements for synergistic transcription directed by a single activator, Bicoid (BCD), bound to multiple sites have been determined. Mutagenesis studies in combination with protein binding experiments and reconstituted transcription reactions identified two independent activation domains of BCD that target different coactivator subunits (TAFII110 and TAFII60) of the basal transcription factor IID (TFIID). The presence of both coactivators is required for BCD to recruit the TATA binding protein (TBP)-TAF complex to the promoter and direct synergistic activation of transcription. Thus, contact between multiple activation domains of BCD and different targets within the TFIID complex can mediate transcriptional synergism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sauer, F -- Hansen, S K -- Tjian, R -- New York, N.Y. -- Science. 1995 Dec 15;270(5243):1825-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8525377" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Line ; DNA/*metabolism ; DNA-Binding Proteins/genetics/metabolism ; Drosophila/*genetics/metabolism ; *Drosophila Proteins ; Enhancer Elements, Genetic ; Escherichia coli ; *Homeodomain Proteins ; Insect Hormones/genetics/*metabolism ; Juvenile Hormones/genetics/metabolism ; Mutagenesis ; Peptide Fragments/genetics/metabolism ; Promoter Regions, Genetic ; Protein Binding ; Recombinant Fusion Proteins/genetics/metabolism ; TATA-Box Binding Protein ; Templates, Genetic ; Trans-Activators/*metabolism ; Transcription Factor TFIID ; Transcription Factors/genetics/metabolism ; *Transcription, Genetic
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  • 72
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-03-24
    Description: Nae I endonuclease must bind to two DNA sequences for cleavage. Examination of the amino acid sequence of Nae I uncovered similarity to the active site of human DNA ligase I, except for leucine 43 in Nae I instead of the lysine essential for ligase activity. Changing leucine 43 to lysine 43 (L43K) changed Nae I activity: Nae I-L43K relaxed supercoiled DNA to yield DNA topoisomers and recombined DNA to give dimeric molecules. Interruption of the reactions of Nae I and Nae I-L43K with DNA demonstrated transient protein-DNA covalent complexes. These findings imply coupled endonuclease and ligase domains and link Nae I endonuclease to the topoisomerase and recombinase protein families.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jo, K -- Topal, M D -- New York, N.Y. -- Science. 1995 Mar 24;267(5205):1817-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, University of North Carolina Medical School, Chapel Hill 27599.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7892605" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; DNA Nucleotidyltransferases/*metabolism ; DNA Topoisomerases, Type I/*metabolism ; DNA, Circular/metabolism ; Deoxyribonucleases, Type II Site-Specific/chemistry/*metabolism ; *Integrases ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Recombinases ; Sequence Homology, Amino Acid
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  • 73
    Publication Date: 1995-12-15
    Description: Evidence suggests that CD8+ T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1 alpha, and MIP-1 beta were identified as the major HIV-SF produced by CD8+ T cells. Two active proteins purified from the culture supernatant of an immortalized CD8+ T cell clone revealed sequence identity with human RANTES and MIP-1 alpha. RANTES, MIP-1 alpha, and MIP-1 beta were released by both immortalized and primary CD8+ T cells. HIV-SF activity produced by these cells was completely blocked by a combination of neutralizing antibodies against RANTES, MIP-1 alpha, and MIP-1 beta. Recombinant human RANTES, MIP-1 alpha, and MIP-1 beta induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). These data may have relevance for the prevention and therapy of AIDS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cocchi, F -- DeVico, A L -- Garzino-Demo, A -- Arya, S K -- Gallo, R C -- Lusso, P -- New York, N.Y. -- Science. 1995 Dec 15;270(5243):1811-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8525373" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Amino Acid Sequence ; Animals ; Antiviral Agents/*physiology ; CD8-Positive T-Lymphocytes/*immunology ; Cell Division/physiology ; Cell Line ; Cells, Cultured ; Chemokine CCL4 ; Chemokine CCL5/antagonists & inhibitors/*immunology ; Culture Media, Conditioned ; Cytokines/antagonists & inhibitors/*immunology ; Dose-Response Relationship, Immunologic ; Escherichia coli ; HIV Infections/immunology ; HIV-1/*immunology ; HIV-2/immunology ; Herpesvirus 6, Human/immunology ; Herpesvirus 7, Human/immunology ; Human T-lymphotropic virus 1/immunology ; Humans ; Immunoglobulin G/immunology ; Lymphocyte Activation ; Macaca nemestrina ; Macrophage Inflammatory Proteins ; Molecular Sequence Data ; Monokines/antagonists & inhibitors/*immunology ; Recombinant Proteins/immunology ; Simian Immunodeficiency Virus/immunology
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  • 74
    Publication Date: 1995-11-17
    Description: Interferon gamma (IFN-gamma) responsiveness in certain cells depends on the state of cellular differentiation or activation. Here an in vitro developmental system was used to show that IFN-gamma produced during generation of the CD4+ T helper cell type 1 (TH1) subset extinguishes expression of the IFN-gamma receptor beta subunit, resulting in TH1 cells that are unresponsive to IFN-gamma. This beta chain loss also occurred in IFN-gamma-treated TH2 cells and thus represents a specific response of CD4+ T cells to IFN-gamma rather than a TH1-specific differentiation event. These results define a mechanism of cellular desensitization where a cytokine down-regulates expression of a receptor subunit required primarily for signaling and not ligand binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bach, E A -- Szabo, S J -- Dighe, A S -- Ashkenazi, A -- Aguet, M -- Murphy, K M -- Schreiber, R D -- New York, N.Y. -- Science. 1995 Nov 17;270(5239):1215-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7502050" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/*biosynthesis ; Cell Differentiation ; Cell Line ; Cytokines/biosynthesis ; Down-Regulation ; Gene Expression ; Genes, MHC Class I ; Interferon-gamma/*pharmacology ; Ligands ; Mice ; Mice, Transgenic ; Receptors, Interferon/*biosynthesis ; Th1 Cells/cytology/immunology/*metabolism ; Th2 Cells/cytology/immunology/*metabolism
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  • 75
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-08-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schepartz, A -- New York, N.Y. -- Science. 1995 Aug 18;269(5226):989-90.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7638626" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; DNA/*chemistry ; *DNA-Binding Proteins ; *Nucleic Acid Conformation ; Repressor Proteins/*chemistry/metabolism ; Thermodynamics ; Viral Proteins ; Viral Regulatory and Accessory Proteins
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-08-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, R F -- New York, N.Y. -- Science. 1995 Aug 18;269(5226):921-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7638612" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Carbon Monoxide/*chemistry/metabolism ; Crystallography, X-Ray ; Heme/metabolism ; Myoglobin/*chemistry/metabolism ; Oxygen/*metabolism ; Spectrophotometry, Infrared ; Water/metabolism
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  • 77
    Publication Date: 1995-05-26
    Description: Src homology 2 (SH2) domains mediate assembly of signaling complexes by binding specifically to tyrosine-phosphorylated proteins. A phosphotyrosine binding (PTB) domain has been identified which also binds specifically to tyrosine-phosphorylated targets, but is structurally different from SH2 domains. Expression cloning was used to identify targets of PTB domains. PTB domains bound to phosphotyrosine within a sequence motif, asparagine-X1-X2-phosphotyrosine (where X represents any amino acid), that is found in many signaling proteins and is not recognized by SH2 domains. Mutational studies indicated that high affinity binding of PTB domains may require a specific conformation of the motif.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kavanaugh, W M -- Turck, C W -- Williams, L T -- K11 HL02714/HL/NHLBI NIH HHS/ -- R01 HL 32898/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1995 May 26;268(5214):1177-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California, San Francisco 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7539155" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites/physiology ; Binding, Competitive ; Cell Line ; Humans ; Molecular Sequence Data ; Phosphopeptides/*metabolism ; Phosphotyrosine ; Protein Binding/*physiology ; Recombinant Proteins/metabolism ; Signal Transduction/*physiology ; Tumor Cells, Cultured ; Tyrosine/*analogs & derivatives/metabolism
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  • 78
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-09-01
    Description: Members of the Rho family of small guanosine triphosphatases (GTPases) regulate the organization of the actin cytoskeleton; Rho controls the assembly of actin stress fibers and focal adhesion complexes, Rac regulates actin filament accumulation at the plasma membrane to produce lamellipodia and membrane ruffles, and Cdc42 stimulates the formation of filopodia. When microinjected into quiescent fibroblasts, Rho, Rac, and Cdc42 stimulated cell cycle progression through G1 and subsequent DNA synthesis. Furthermore, microinjection of dominant negative forms of Rac and Cdc42 or of the Rho inhibitor C3 transferase blocked serum-induced DNA synthesis. Unlike Ras, none of the Rho GTPases activated the mitogen-activated protein kinase (MAPK) cascade that contains the protein kinases c-Raf1, MEK (MAPK or ERK kinase), and ERK (extracellular signal-regulated kinase). Instead, Rac and Cdc42, but not Rho, stimulated a distinct MAP kinase, the c-Jun kinase JNK/SAPK (Jun NH2-terminal kinase or stress-activated protein kinase). Rho, Rac, and Cdc42 control signal transduction pathways that are essential for cell growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olson, M F -- Ashworth, A -- Hall, A -- New York, N.Y. -- Science. 1995 Sep 1;269(5228):1270-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University College, London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7652575" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Amino Acid Sequence ; Animals ; Base Sequence ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Cell Cycle Proteins/*metabolism ; Cell Line ; DNA/biosynthesis ; *G1 Phase ; GTP Phosphohydrolases/*metabolism ; GTP-Binding Proteins/*metabolism ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Kinase 1 ; Mice ; Microinjections ; *Mitogen-Activated Protein Kinase Kinases ; *Mitogen-Activated Protein Kinases ; Molecular Sequence Data ; Protein-Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-raf ; *Signal Transduction ; Transfection ; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae ; rac GTP-Binding Proteins ; rhoA GTP-Binding Protein
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  • 79
    Publication Date: 1995-06-09
    Description: Macrocyclic polyketides exhibit an impressive range of medically useful activities, and there is great interest in manipulating the genes that govern their synthesis. The 6-deoxyerythronolide B synthase (DEBS) of Saccharopolyspora erythraea, which synthesizes the aglycone core of the antibiotic erythromycin A, has been modified by repositioning of a chain-terminating cyclase domain to the carboxyl-terminus of DEBS1, the multienzyme that catalyzes the first two rounds of polyketide chain extension. The resulting mutant markedly accelerates formation of the predicted triketide lactone, compared to a control in which the repositioned domain is inactive. Repositioning of the cyclase should be generally useful for redirecting polyketide synthesis to obtain polyketides of specified chain lengths.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cortes, J -- Wiesmann, K E -- Roberts, G A -- Brown, M J -- Staunton, J -- Leadlay, P F -- New York, N.Y. -- Science. 1995 Jun 9;268(5216):1487-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cambridge Centre for Molecular Recognition, University of Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7770773" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Cloning, Molecular ; Erythromycin/biosynthesis ; Genes, Bacterial ; Genetic Vectors ; Molecular Sequence Data ; Multienzyme Complexes/chemistry/genetics/*metabolism ; *Protein Engineering ; Saccharopolyspora/*enzymology/genetics ; Transformation, Genetic
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  • 80
    Publication Date: 1995-04-14
    Description: Coligation of the Fc receptor on B cells, Fc gamma RIIB1, with the B cell antigen receptor (BCR) leads to abortive BCR signaling. Here it was shown that the Fc gamma RIIB1 recruits the phosphotyrosine phosphatase PTP1C after BCR coligation. This association is mediated by the binding of a 13-amino acid tyrosine-phosphorylated sequence to the carboxyl-terminal Src homology 2 domain of PTP1C and activates PTP1C. Inhibitory signaling and PTP1C recruitment are dependent on the presence of the tyrosine within the 13-amino acid sequence. Inhibitory signaling mediated by Fc gamma RIIB1 is deficient in motheaten mice which do not express functional PTP1C. Thus, PTP1C is an effector of BCR-Fc gamma RIIB1 negative signal cooperativity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉D'Ambrosio, D -- Hippen, K L -- Minskoff, S A -- Mellman, I -- Pani, G -- Siminovitch, K A -- Cambier, J C -- New York, N.Y. -- Science. 1995 Apr 14;268(5208):293-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7716523" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibody Formation ; *Antigens, CD ; B-Lymphocytes/*immunology/metabolism ; Binding Sites ; Calcium/metabolism ; Intracellular Signaling Peptides and Proteins ; Mice ; Mice, Mutant Strains ; Molecular Sequence Data ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/*metabolism ; Receptors, Antigen, B-Cell/*metabolism ; Receptors, IgG/*metabolism ; *Signal Transduction ; Tumor Cells, Cultured
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  • 81
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-10-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Craig, N L -- New York, N.Y. -- Science. 1995 Oct 13;270(5234):253-4.〈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, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569973" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry/metabolism ; Bacteriophage mu/*genetics/physiology ; Binding Sites ; DNA Nucleotidyltransferases/chemistry/metabolism ; DNA Repair ; *DNA Transposable Elements ; DNA, Viral/metabolism ; Endodeoxyribonucleases/chemistry/metabolism ; *Escherichia coli Proteins ; Integrases ; Nucleotidyltransferases/chemistry/metabolism ; Recombination, Genetic ; Retroviridae/*genetics/physiology ; Ribonuclease H/chemistry/metabolism ; Transposases ; Virus Integration ; Virus Replication
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  • 82
    Publication Date: 1995-10-06
    Description: Fundamental chemical transformations for biogeochemical cycling of sulfur and nitrogen are catalyzed by sulfite and nitrite reductases. The crystallographic structure of Escherichia coli sulfite reductase hemoprotein (SiRHP), which catalyzes the concerted six-electron reductions of sulfite to sulfide and nitrite to ammonia, was solved with multiwavelength anomalous diffraction (MAD) of the native siroheme and Fe4S4 cluster cofactors, multiple isomorphous replacement, and selenomethionine sequence markers. Twofold symmetry within the 64-kilodalton polypeptide generates a distinctive three-domain alpha/beta fold that controls cofactor assembly and reactivity. Homology regions conserved between the symmetry-related halves of SiRHP and among other sulfite and nitrite reductases revealed key residues for stability and function, and identified a sulfite or nitrite reductase repeat (SNiRR) common to a redox-enzyme superfamily. The saddle-shaped siroheme shares a cysteine thiolate ligand with the Fe4S4 cluster and ligates an unexpected phosphate anion. In the substrate complex, sulfite displaces phosphate and binds to siroheme iron through sulfur. An extensive hydrogen-bonding network of positive side chains, water molecules, and siroheme carboxylates activates S-O bonds for reductive cleavage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crane, B R -- Siegel, L M -- Getzoff, E D -- GM212226/GM/NIGMS NIH HHS/ -- GM37684/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Oct 6;270(5233):59-67.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569952" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anions ; Binding Sites ; Catalysis ; Computer Graphics ; Crystallography, X-Ray ; Escherichia coli/*enzymology ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidoreductases Acting on Sulfur Group Donors/*chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sulfite Reductase (NADPH) ; Sulfites/*metabolism
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  • 83
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-04-14
    Description: Zinc finger proteins of the Cys2His2 type represent a large class of proteins that have been assumed to function by means of specific interactions with DNA. Experiments motivated by structural characteristics of zinc finger protein-DNA complexes revealed that certain zinc finger proteins bound DNA-RNA hybrids with affinities comparable to or greater than those for DNA duplexes. The interactions between the zinc finger proteins and the DNA-RNA hybrids were dependent on which strand was RNA and were sequence-specific. Thus, interactions with DNA-RNA hybrids should be considered with regard to the biological roles of zinc finger proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, Y -- Berg, J M -- GM46257/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Apr 14;268(5208):282-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7536342" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; DNA/chemistry/*metabolism ; Molecular Sequence Data ; Nucleic Acid Hybridization ; RNA/chemistry/*metabolism ; RNA-Binding Proteins/chemistry/*metabolism ; Sp1 Transcription Factor/metabolism ; Zinc Fingers/*physiology
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  • 84
    Publication Date: 1995-09-22
    Description: Activation of early response genes by interferons (IFNs) requires tyrosine phosphorylation of STAT (signal transducers and activators of transcription) proteins. It was found that the serine-threonine kinase mitogen-activated protein kinase (MAPK) [specifically, the 42-kilodalton MAPK or extracellular signal-regulated kinase 2 (ERK2)] interacted with the alpha subunit of IFN-alpha/beta receptor in vitro and in vivo. Treatment of cells with IFN-beta induced tyrosine phosphorylation and activation of MAPK and caused MAPK and Stat1 alpha to coimmunoprecipitate. Furthermore, expression of dominant negative MAPK inhibited IFN-beta-induced transcription. Therefore, MAPK appears to regulate IFN-alpha and IFN-beta activation of early response genes by modifying the Jak-STAT signaling cascade.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉David, M -- Petricoin, E 3rd -- Benjamin, C -- Pine, R -- Weber, M J -- Larner, A C -- GM47332/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Sep 22;269(5231):1721-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cytokine Biology, Center for Biologics Evaluation and Research, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569900" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Calcium-Calmodulin-Dependent Protein Kinases/*metabolism ; Cells, Cultured ; DNA-Binding Proteins/*metabolism ; Enzyme Activation ; *Gene Expression Regulation ; Humans ; Interferon-alpha/pharmacology ; Interferon-beta/*pharmacology ; Membrane Proteins ; Mitogen-Activated Protein Kinase 1 ; Phosphorylation ; Receptor, Interferon alpha-beta ; Receptors, Interferon/*metabolism ; Recombinant Fusion Proteins/metabolism ; STAT1 Transcription Factor ; *Signal Transduction ; Trans-Activators/*metabolism ; Transcription, Genetic ; Transfection ; Tumor Cells, Cultured ; Tyrosine/metabolism
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  • 85
    Publication Date: 1995-07-07
    Description: The crystal structure of an aminimide analog of a dipeptide inhibitor of porcine pancreatic elastase bound to its target serine protease has been solved. The peptidomimetic molecule binds in the same fashion as the class of dipeptides from which it was derived, making similar interactions with the subsites on the elastase surface. Because aminimides are readily synthesized from a wide variety of starting materials, they form the basis for a combinatorial chemistry approach to rational drug design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peisach, E -- Casebier, D -- Gallion, S L -- Furth, P -- Petsko, G A -- Hogan, J C Jr -- Ringe, D -- T32GMO7596/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Jul 7;269(5220):66-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Biophysics, Brandeis University, Waltham, MA 02254, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7604279" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anilides/chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; Dipeptides/chemistry/*metabolism ; Hydrazines/chemistry/*metabolism ; Hydrogen Bonding ; Molecular Sequence Data ; Pancreatic Elastase/*antagonists & inhibitors/chemistry/metabolism
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  • 86
    Publication Date: 1995-02-24
    Description: Severe combined immunodeficient (SCID) mice are deficient in a recombination process utilized in both DNA double-strand break repair and in V(D)J recombination. The phenotype of these mice involves both cellular hypersensitivity to ionizing radiation and a lack of B and T cell immunity. The catalytic subunit of DNA-dependent protein kinase, p350, was identified as a strong candidate for the murine gene SCID. Both p350 and a gene complementing the SCID defect colocalize to human chromosome 8q11. Chromosomal fragments expressing p350 complement the SCID phenotype, and p350 protein levels are greatly reduced in cells derived from SCID mice compared to cells from wild-type mice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kirchgessner, C U -- Patil, C K -- Evans, J W -- Cuomo, C A -- Fried, L M -- Carter, T -- Oettinger, M A -- Brown, J M -- CA 15201/CA/NCI NIH HHS/ -- CA 37761/CA/NCI NIH HHS/ -- GM48026/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Feb 24;267(5201):1178-83.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7855601" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Chromosome Mapping ; Chromosomes, Human, Pair 8 ; Cloning, Molecular ; DNA Repair/genetics ; DNA-Activated Protein Kinase ; *DNA-Binding Proteins ; Gamma Rays ; Genetic Complementation Test ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence ; Mice ; Mice, SCID ; Molecular Sequence Data ; Nuclear Proteins ; Phenotype ; Protein-Serine-Threonine Kinases/*genetics/metabolism ; Radiation Tolerance ; Recombination, Genetic ; Severe Combined Immunodeficiency/enzymology/*genetics
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  • 87
    Publication Date: 1995-07-14
    Description: It has long been the paradigm that T cells recognize peptide antigens presented by major histocompatibility complex (MHC) molecules. However, nonpeptide antigens can be presented to T cells by human CD1b molecules, which are not encoded by the MHC. A major class of microbial antigens associated with pathogenicity are lipoglycans. It is shown here that human CD1b presents the defined mycobacterial lipoglycan lipoarabinomannan (LAM) to alpha beta T cell receptor-bearing lymphocytes. Presentation of these lipoglycan antigens required internalization and endosomal acidification. The T cell recognition required mannosides with alpha(1--〉2) linkages and a phosphotidylinositol unit. T cells activated by LAM produced interferon gamma and were cytolytic. Thus, an important class of microbial molecules, the lipoglycans, is a part of the universe of foreign antigens recognized by human T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sieling, P A -- Chatterjee, D -- Porcelli, S A -- Prigozy, T I -- Mazzaccaro, R J -- Soriano, T -- Bloom, B R -- Brenner, M B -- Kronenberg, M -- Brennan, P J -- AI 07118/AI/NIAID NIH HHS/ -- AI 18357/AI/NIAID NIH HHS/ -- AI 28973/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1995 Jul 14;269(5221):227-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Dermatology, University of California at Los Angeles (UCLA) School of Medicine 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7542404" target="_blank"〉PubMed〈/a〉
    Keywords: *Antigen Presentation ; Antigen-Presenting Cells/immunology ; Antigens, CD/*immunology ; Antigens, CD1 ; Carbohydrate Conformation ; Carbohydrate Sequence ; Cell Line ; Humans ; Interferon-gamma/secretion ; Interleukin-4/secretion ; Leprosy/*immunology ; Lipopolysaccharides/*immunology ; Lymphocyte Activation ; Molecular Sequence Data ; Mycobacterium leprae/immunology ; Phosphatidylinositols/immunology ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Species Specificity ; T-Lymphocytes, Cytotoxic/*immunology
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  • 88
    Publication Date: 1995-09-15
    Description: H-Y is a transplantation antigen that can lead to rejection of male organ and bone marrow grafts by female recipients, even if the donor and recipient match at the major histocompatibility locus of humans, the HLA (human leukocyte antigen) locus. However, the origin and function of H-Y antigens has eluded researchers for 40 years. One human H-Y antigen presented by HLA-B7 was identified as an 11-residue peptide derived from SMCY, an evolutionarily conserved protein encoded on the Y chromosome. The protein from the homologous gene on the X chromosome, SMCX, differs by two amino acid residues in the same region. The identification of H-Y may aid in transplantation prognosis, prenatal diagnosis, and fertilization strategies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, W -- Meadows, L R -- den Haan, J M -- Sherman, N E -- Chen, Y -- Blokland, E -- Shabanowitz, J -- Agulnik, A I -- Hendrickson, R C -- Bishop, C E -- AI20963/AI/NIAID NIH HHS/ -- AI33993/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1995 Sep 15;269(5230):1588-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Virginia, Charlottesville 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7667640" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; B-Lymphocytes ; Cell Line ; Chromatography, High Pressure Liquid ; H-Y Antigen/*chemistry/genetics/immunology ; HLA-B7 Antigen/immunology ; Histone Demethylases ; Histone-Lysine N-Methyltransferase ; Humans ; Male ; Mass Spectrometry/methods ; Molecular Sequence Data ; Molecular Weight ; Oxidoreductases, N-Demethylating ; Proteins/*chemistry/genetics/immunology ; T-Lymphocytes, Cytotoxic/immunology ; X Chromosome ; *Y Chromosome
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  • 89
    Publication Date: 1995-12-01
    Description: Intracellular calcium (Ca2+) inhibits the opening of L-type (alpha 1C) Ca2+ channels, providing physiological control of Ca2+ entry into a wide variety of cells. A structural determinant of this Ca(2+)-sensitive inactivation was revealed by chimeric Ca2+ channels derived from parental alpha 1C and alpha 1E channels, the latter of which is a neuronal channel lacking Ca2+ inactivation. A consensus Ca(2+)-binding motif (an EF hand), located on the alpha 1C subunit, was required for Ca2+ inactivation. Donation of the alpha 1C EF-hand region to the alpha 1E channel conferred the Ca(2+)-inactivating phenotype. These results strongly suggest that Ca2+ binding to the alpha 1C subunit initiates Ca2+ inactivation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Leon, M -- Wang, Y -- Jones, L -- Perez-Reyes, E -- Wei, X -- Soong, T W -- Snutch, T P -- Yue, D T -- New York, N.Y. -- Science. 1995 Dec 1;270(5241):1502-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7491499" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Barium/metabolism ; Calcium/*metabolism/pharmacology ; Calcium Channels/chemistry/*metabolism ; Cell Line ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Humans ; Ion Channel Gating ; Molecular Sequence Data ; Patch-Clamp Techniques ; Phosphorylation ; Recombinant Fusion Proteins/chemistry/metabolism ; Sequence Alignment ; Up-Regulation
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  • 90
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-07-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warshel, A -- Papazyan, A -- Kollman, P A -- New York, N.Y. -- Science. 1995 Jul 7;269(5220):102-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7661987" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; *Catalysis ; Chemistry, Physical ; Enzymes/*metabolism ; *Hydrogen Bonding ; Hydrogen-Ion Concentration ; Physicochemical Phenomena
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  • 91
    Publication Date: 1995-09-29
    Description: Conformational changes, including local protein folding, play important roles in protein-DNA interactions. Here, studies of the transcription factor Ets-1 provided evidence that local protein unfolding also can accompany DNA binding. Circular dichroism and partial proteolysis showed that the secondary structure of the Ets-1 DNA-binding domain is unchanged in the presence of DNA. In contrast, DNA allosterically induced the unfolding of an alpha helix that lies within a flanking region involved in the negative regulation of DNA binding. These findings suggest a structural basis for the intramolecular inhibition of DNA binding and a mechanism for the cooperative partnerships that are common features of many eukaryotic transcription factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petersen, J M -- Skalicky, J J -- Donaldson, L W -- McIntosh, L P -- Alber, T -- Graves, B J -- CA 42014/CA/NCI NIH HHS/ -- GM 48958/GM/NIGMS NIH HHS/ -- GM38663/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Sep 29;269(5232):1866-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City 84132, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569926" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Circular Dichroism ; DNA/chemistry/*metabolism ; Molecular Sequence Data ; Protein Binding ; Protein Conformation ; *Protein Folding ; *Protein Structure, Secondary ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Proteins/chemistry/*metabolism ; Proto-Oncogene Proteins c-ets ; Transcription Factors/chemistry/*metabolism
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  • 92
    Publication Date: 1995-07-21
    Description: The basal lamina that ensheaths skeletal muscle fibers traverses the synaptic cleft at the neuromuscular junction. Synaptic and extrasynaptic portions of the basal lamina contain different laminin beta chains: beta 2 (or s) at synapses and beta 1 (or B1) extrasynaptically. Laminin beta 2 is also confined to synapselike patches on myotube surfaces in vitro, whereas beta 1 is present throughout the extracellular matrix. This differential localization of laminin beta chains was analyzed by expression of chimeric beta 1-beta 2 molecules in cultured mouse myotubes. A 16-amino acid carboxyl-terminal sequence in beta 2 was necessary for synaptic localization, and an amino-terminal domain in beta 1 promoted association with extracellular fibrils. The synaptic targeting sequence of beta 2 contains a site previously shown to be adhesive for motor neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martin, P T -- Ettinger, A J -- Sanes, J R -- New York, N.Y. -- Science. 1995 Jul 21;269(5222):413-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Neurobiology, Washington University School of Medicine, St.Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7618109" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Basement Membrane/chemistry/metabolism ; Cell Line ; Laminin/analysis/biosynthesis/*chemistry/*metabolism ; Mice ; Molecular Sequence Data ; Muscle, Skeletal/cytology/metabolism ; Neuromuscular Junction/chemistry/metabolism ; Oligopeptides/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Cholinergic/analysis ; Recombinant Fusion Proteins/chemistry/metabolism ; Synapses/chemistry/*metabolism ; Transfection
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  • 93
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-08-18
    Description: Protein reaction kinetics in aqueous solution at room temperature are often simplified by the thermal averaging of conformational substates. These substates exhibit widely varying reaction rates that are usually exposed by trapping in a glass at low temperature. Here, it is shown that the solvent viscosity, rather than the low temperature, is primarily responsible for the trapping. This was demonstrated by placement of myoglobin in a glass at room temperature and subsequent observation of inhomogeneous reaction kinetics. The high solvent viscosity slowed the rate of crossing the energy barriers that separated the substates and also suppressed any change in the average protein conformation after ligand dissociation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagen, S J -- Hofrichter, J -- Eaton, W A -- New York, N.Y. -- Science. 1995 Aug 18;269(5226):959-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chemical Physics, National Institutes of Health, Bethesda, MD 20892-0520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7638618" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Carbon Monoxide/*chemistry/metabolism ; Glass ; Kinetics ; Ligands ; Myoglobin/*chemistry/metabolism ; Photolysis ; Protein Conformation ; Spectrum Analysis ; Temperature ; Trehalose ; Viscosity
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  • 94
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-07-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martin, S J -- McGahon, A J -- Nishioka, W K -- LaFace, D -- Guo, X -- Th'ng, J -- Bradbury, E M -- Green, D R -- GM52735/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Jul 7;269(5220):106-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7604270" target="_blank"〉PubMed〈/a〉
    Keywords: *Apoptosis ; CDC2 Protein Kinase/*metabolism ; Cell Line ; Temperature
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  • 95
    Publication Date: 1995-05-26
    Description: In higher eukaryotes, the polypyrimidine-tract (Py-tract) adjacent to the 3' splice site is recognized by several proteins, including the essential splicing factor U2AF65, the splicing regulator Sex-lethal (Sxl), and polypyrimidine tract-binding protein (PTB), whose function is unknown. Iterative in vitro genetic selection was used to show that these proteins have distinct sequence preferences. The uridine-rich degenerate sequences selected by U2AF65 are similar to those present in the diverse array of natural metazoan Py-tracts. In contrast, the Sxl-consensus is a highly specific sequence, which can help explain the ability of Sxl to regulate splicing of transformer pre-mRNA and autoregulate splicing of its own pre-mRNA. The PTB-consensus is not a typical Py-tract; it can be found in certain alternatively spliced pre-mRNAs that undergo negative regulation. Here it is shown that PTB can regulate alternative splicing by selectively repressing 3' splice sites that contain a PTB-binding site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Singh, R -- Valcarcel, J -- Green, M R -- New York, N.Y. -- Science. 1995 May 26;268(5214):1173-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7761834" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Consensus Sequence ; DNA, Complementary ; Drosophila ; *Drosophila Proteins ; Female ; Humans ; Insect Hormones/metabolism ; Male ; Molecular Sequence Data ; *Nuclear Proteins ; Polypyrimidine Tract-Binding Protein ; *RNA Splicing ; RNA-Binding Proteins/*metabolism ; Ribonucleoproteins/*metabolism
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  • 96
    Publication Date: 1995-10-06
    Description: The activation of cyclin-dependent kinases (CDKs) requires the phosphorylation of a conserved threonine (Thr160 in Cdk2) by CDK-activating kinase (CAK). Human KAP (also called Cdi1), a CDK-associated phosphatase, was shown to dephosphorylate Thr160 in human Cdk2. KAP was unable to dephosphorylate Tyr15 and only dephosphorylated Thr160 in native monomeric Cdk2. The binding of cyclin A to Cdk2 inhibited the dephosphorylation of Thr160 by KAP but did not preclude the binding of KAP to the cyclin A-Cdk2 complex. Moreover, the dephosphorylation of Thr160 by KAP prevented Cdk2 kinase activity upon subsequent association with cyclin A. These results suggest that KAP binds to Cdk2 and dephosphorylates Thr160 when the associated cyclin subunit is degraded or dissociates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poon, R Y -- Hunter, T -- CA14195/CA/NCI NIH HHS/ -- CA39780/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1995 Oct 6;270(5233):90-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037-1099, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7569954" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; *CDC2-CDC28 Kinases ; *Cell Cycle Proteins ; Cell Line ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinase Inhibitor Proteins ; Cyclin-Dependent Kinases/*metabolism ; Cyclins/metabolism ; Dual-Specificity Phosphatases ; HeLa Cells ; Humans ; Molecular Sequence Data ; Phosphoprotein Phosphatases/*metabolism ; Phosphorylation ; *Protein Tyrosine Phosphatases ; Protein-Serine-Threonine Kinases/*metabolism ; Recombinant Fusion Proteins/metabolism ; Threonine/metabolism
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  • 97
    Publication Date: 1995-02-17
    Description: The mechanism of inhibition of HIV-1 reverse transcriptase by three nonnucleoside inhibitors is described. Nevirapine, O-TIBO, and CI-TIBO each bind to a hydrophobic pocket in the enzyme-DNA complex close to the active site catalytic residues. Pre-steady-state kinetic analysis was used to establish the mechanism of inhibition by these noncompetitive inhibitors. Analysis of the pre-steady-state burst of DNA polymerization indicated that inhibitors blocked the chemical reaction, but did not interfere with nucleotide binding or the nucleotide-induced conformational change. Rather, in the presence of saturating concentrations of the inhibitors, the nucleoside triphosphate bound tightly (Kd, 100 nM), but nonproductively. The data suggest that an inhibitor combining the functionalities of a nonnucleoside inhibitor and a nucleotide analog could bind very tightly and specifically to reverse transcriptase and could be effective in the treatment of AIDS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spence, R A -- Kati, W M -- Anderson, K S -- Johnson, K A -- GM44613/GM/NIGMS NIH HHS/ -- GM49551/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1995 Feb 17;267(5200):988-93.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7532321" target="_blank"〉PubMed〈/a〉
    Keywords: Antiviral Agents/metabolism/*pharmacology ; Benzodiazepines/metabolism/*pharmacology ; Binding Sites ; DNA/metabolism ; Deoxyadenine Nucleotides/metabolism ; HIV Reverse Transcriptase ; HIV-1/drug effects/*enzymology ; Imidazoles/metabolism/*pharmacology ; Kinetics ; Magnesium/metabolism/pharmacology ; Nevirapine ; Protein Conformation ; Pyridines/metabolism/*pharmacology ; RNA-Directed DNA Polymerase/chemistry/metabolism ; *Reverse Transcriptase Inhibitors
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  • 98
    Publication Date: 1995-01-13
    Description: Peptides from endogenous proteins are presented by major histocompatibility complex class I molecules, but antigens (Ags) in the extracellular fluids are generally not. However, pathogens or particulate Ags that are internalized into phagosomes of macrophages (M phi s) stimulate CD8 T cells. The presentation of these Ags is resistant to chloroquine but is blocked by inhibitors of the proteasome, a mutation in the TAP1-TAP2 transporter, and brefeldin A. Moreover, phagocytosis of a ribosomal-inactivating protein inhibited M phi protein synthesis. These results demonstrate that M phi s transfer Ags from phagosomes into the cytosol and that endogenous and exogenous Ags use a final common pathway for class I presentation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kovacsovics-Bankowski, M -- Rock, K L -- AI20248/AI/NIAID NIH HHS/ -- AI31337/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1995 Jan 13;267(5195):243-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Lymphocyte Biology, Dana-Farber Cancer Institute, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7809629" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/genetics/metabolism ; Amino Acid Sequence ; Animals ; *Antigen Presentation ; Antigens/*metabolism ; Brefeldin A ; Cell Line ; Chloroquine/pharmacology ; Cyclopentanes/pharmacology ; Cysteine Endopeptidases/metabolism ; Cytosol/*immunology/metabolism ; Histocompatibility Antigens Class I/*immunology ; Macrophages/*immunology ; Mice ; Molecular Sequence Data ; Multienzyme Complexes/metabolism ; Oligopeptides/immunology/metabolism ; Ovalbumin/immunology/metabolism ; Phagocytosis ; Phagosomes/*immunology/metabolism ; Plant Proteins/pharmacology ; Proteasome Endopeptidase Complex ; Ribosome Inactivating Proteins, Type 1
    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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  • 99
    Publication Date: 1995-03-03
    Description: In response to specific ligands, various STAT proteins (signal transducers and activators of transcription) are phosphorylated on tyrosine by Jak protein kinases and translocated to the nucleus to direct gene transcription. Selection of a STAT at the interferon gamma receptor as well as specific STAT dimer formation depended on the presence of particular SH2 groups (phosphotyrosine-binding domains), whereas the amino acid sequence surrounding the phosphorylated tyrosine on the STAT could vary. Thus, SH2 groups in STAT proteins may play crucial roles in specificity at the receptor kinase complex and in subsequent dimerization, whereas the kinases are relatively nonspecific.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heim, M H -- Kerr, I M -- Stark, G R -- Darnell, J E Jr -- AI32489/AI/NIAID NIH HHS/ -- AI34420/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1995 Mar 3;267(5202):1347-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7871432" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; DNA-Binding Proteins/chemistry/*metabolism ; Interferon-alpha/*pharmacology ; Interferon-gamma/*pharmacology ; Janus Kinase 1 ; Janus Kinase 2 ; Phosphorylation ; Protein-Tyrosine Kinases/*metabolism ; Proteins/metabolism ; *Proto-Oncogene Proteins ; Receptors, Interferon/metabolism ; Recombinant Fusion Proteins/metabolism ; STAT1 Transcription Factor ; Signal Transduction ; Trans-Activators/chemistry/*metabolism ; Tyrosine/metabolism
    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
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-11-24
    Description: Some growth factors are therapeutically useful partly because restricted expression of their receptors limits their action to particular cell types. However, no unique stimulatory factor is known for many clinically relevant cell types, such as CD34+ hematopoietic stem cells. Here, soluble alpha receptor (R alpha) components for interleukin-6 (IL-6) and ciliary neurotrophic factor (CNTF) were targeted in an active form to cells expressing surface markers such as CD34 or CD45, thereby rendering those cells responsive to IL-6 or CNTF. The targeting of R alpha components may provide the means to create "designer" cytokines that activate a desired cell type expressing a specific cell surface marker.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Economides, A N -- Ravetch, J V -- Yancopoulos, G D -- Stahl, N -- New York, N.Y. -- Science. 1995 Nov 24;270(5240):1351-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481821" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; Antigens, CD/immunology/*metabolism ; Antigens, CD34/analysis ; Antigens, CD45/analysis ; Cell Division ; Cell Line ; Cell Membrane/*metabolism ; Ciliary Neurotrophic Factor ; Cytokine Receptor gp130 ; *Growth Inhibitors ; Humans ; Immunoglobulin Fc Fragments ; Interleukin-6/*pharmacology ; Leukemia Inhibitory Factor ; Leukemia Inhibitory Factor Receptor alpha Subunit ; *Lymphokines ; Membrane Glycoproteins/metabolism ; Nerve Tissue Proteins/*pharmacology ; Phosphorylation ; Receptor, Ciliary Neurotrophic Factor ; Receptors, Cytokine/metabolism ; Receptors, Fc ; Receptors, Interleukin/immunology/*metabolism ; Receptors, Interleukin-6 ; Receptors, Nerve Growth Factor/immunology/*metabolism ; Receptors, OSM-LIF ; Recombinant Fusion Proteins/metabolism ; Solubility ; Tumor Cells, Cultured
    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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