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  • Protein Conformation  (61)
  • Chemistry
  • Fisheries
  • Inorganic Chemistry
  • American Association for the Advancement of Science (AAAS)  (68)
  • AGU
  • 2005-2009
  • 1990-1994  (68)
  • 1990  (68)
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  • 2005-2009
  • 1990-1994  (68)
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  • 1
    Publication Date: 1990-08-17
    Description: The transcription factor C/EBP uses a bipartite structural motif to bind DNA. Two protein chains dimerize through a set of amphipathic alpha helices termed the leucine zipper. Highly basic polypeptide regions emerge from the zipper to form a linked set of DNA contact surfaces. In the recently proposed a "scissors grip" model, the paired set of basic regions begin DNA contact at a central point and track in opposite directions along the major groove, forming a molecular clamp around DNA. This model predicts that C/EBP must undertake significant changes in protein conformation as it binds and releases DNA. The basic region of ligand-free C/EBP is highly sensitive to protease digestion. Pronounced resistance to proteolysis occurred when C/EBP associated with its specific DNA substrate. Sequencing of discrete proteolytic fragments showed that prominent sites for proteolysis occur at two junction points predicted by the "scissors grip" model. One junction corresponds to the cleft where the basic regions emerge from the leucine zipper. The other corresponds to a localized nonhelical segment that has been hypothesized to contain an N-cap and facilitate the sharp angulation necessary for the basic region to track continuously in the major groove of DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shuman, J D -- Vinson, C R -- McKnight, S L -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):771-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Research Laboratories, Department of Embryology, Baltimore, MD 21210.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2202050" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; CCAAT-Enhancer-Binding Proteins ; Chromatography, High Pressure Liquid ; DNA/*metabolism ; DNA-Binding Proteins/metabolism ; Kinetics ; Leucine ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Nuclear Proteins/*metabolism ; Peptide Fragments/metabolism ; Peptide Hydrolases/*metabolism ; Protein Conformation ; Transcription Factors/*metabolism ; Trypsin/metabolism
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  • 2
    Publication Date: 1990-05-18
    Description: The 70-kilodalton family of heat shock proteins (Hsp 70) has been implicated in posttranslational protein assembly and translocation. Binding of cytosolic forms of Hsp 70 (Hsp 72,73) with nascent proteins in the normal cell was investigated and found to be transient and adenosine triphosphate (ATP)-dependent. Interaction of Hsp 72,73 with newly synthesized proteins appeared to occur cotranslationally, because nascent polypeptides released prematurely from polysomes in vivo can be isolated in a complex with Hsp 72,73. Moreover, isolation of polysomes from short-term [35S]Met-labeled cells (pulsed) revealed that Hsp 72,73 associated with nascent polypeptide chains. In cells experiencing stress, newly synthesized proteins coimmunoprecipitated with Hsp 72,73; however, in contrast to normal cells, interaction with Hsp 72,73 was not transient. A model consistent with these data suggests that under normal growth conditions, cytosolic Hsp 72,73 interact transiently with nascent polypeptides to facilitate proper folding, and that metabolic stress interferes with these events.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beckmann, R P -- Mizzen, L E -- Welch, W J -- GM 33551/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 May 18;248(4957):850-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2188360" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Azetidinecarboxylic Acid/pharmacology ; Cycloheximide/pharmacology ; HeLa Cells/metabolism ; Heat-Shock Proteins/*metabolism ; Humans ; Immunosorbent Techniques ; Macromolecular Substances ; Molecular Weight ; *Protein Biosynthesis ; Protein Conformation ; Protein Processing, Post-Translational ; Proteins/metabolism ; Puromycin/pharmacology
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  • 3
    Publication Date: 1990-05-18
    Description: Most proteins destined for export from Escherichia coli are made as precursors containing amino-terminal leader sequences that are essential for export and that are removed during the process. The initial step in export of a subset of proteins, which includes maltose-binding protein, is binding of the precursor by the molecular chaperone SecB. This work shows directly that SecB binds with high affinity to unfolded maltose-binding protein but does not specifically recognize and bind the leader. Rather, the leader modulates folding to expose elements in the remainder of the polypeptide that are recognized by SecB.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Randall, L L -- Topping, T B -- Hardy, S J -- GM 29798/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 May 18;248(4957):860-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemistry/Biophysics Program, Washington State University, Pullman 99164-4660.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2188362" target="_blank"〉PubMed〈/a〉
    Keywords: *ATP-Binding Cassette Transporters ; Bacterial Proteins/*metabolism ; Binding Sites ; Biological Transport ; Carrier Proteins/*metabolism ; Cytosol/metabolism ; Escherichia coli/*metabolism ; *Escherichia coli Proteins ; Maltose-Binding Proteins ; Molecular Weight ; *Monosaccharide Transport Proteins ; Protein Conformation ; Protein Precursors/*metabolism ; Protein Sorting Signals/*metabolism
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  • 4
    Publication Date: 1990-02-16
    Description: The complex formed in solution by native and chemically modified cytochrome c with cytochrome b5 has been studied by 1H and 13C nuclear magnetic resonance spectroscopy (NMR). Contrary to predictions of recent theoretical analysis, 1H NMR spectroscopy indicates that there is no major movement of cytochrome c residue Phe82 on binding to cytochrome b5. The greater resolution provided by 13C NMR spectroscopy permits detection of small perturbations in the environments of cytochrome c residues Ile75 and Ile85 on binding with cytochrome b5, a result that is in agreement with earlier model-building experiments. As individual cytochrome c lysyl residues are resolved in the 1H NMR spectrum of N-acetimidylated cytochrome c, the interaction of this modified protein with cytochrome b5 has been studied to evaluate the number of cytochrome c lysyl residues involved in binding to cytochrome b5. The results of this experiment indicate that at least six lysyl residues are involved, two more than predicted by static model building, which indicates that cytochrome c and cytochrome b5 form two or more structurally similar 1:1 complexes in solution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burch, A M -- Rigby, S E -- Funk, W D -- MacGillivray, R T -- Mauk, M R -- Mauk, A G -- Moore, G R -- GM-28834/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Feb 16;247(4944):831-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemical Sciences, University of East Anglia, Norwich, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2154849" target="_blank"〉PubMed〈/a〉
    Keywords: Carbon Isotopes ; Cytochrome c Group/*metabolism ; Cytochromes b5/*metabolism ; Hydrogen ; Magnetic Resonance Spectroscopy/methods ; Protein Binding ; Protein Conformation ; Surface Properties
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  • 5
    Publication Date: 1990-03-09
    Description: An antibody to a platelet integral membrane glycoprotein was found to cross-react with the previously identified CD31 myelomonocytic differentiation antigen and with hec7, an endothelial cell protein that is enriched at intercellular junctions. This antibody identified a complementary DNA clone from an endothelial cell library. The 130-kilodalton translated sequence contained six extracellular immunoglobulin (Ig)-like domains and was most similar to the cell adhesion molecule (CAM) subgroup of the Ig superfamily. This is the only known member of the CAM family on platelets. Its cell surface distribution suggests participation in cellular recognition events.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newman, P J -- Berndt, M C -- Gorski, J -- White, G C 2nd -- Lyman, S -- Paddock, C -- Muller, W A -- HL-40926/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Mar 9;247(4947):1219-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Blood Center of Southeastern Wisconsin, Milwaukee 53233.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1690453" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antibodies, Monoclonal ; Antigens, CD31 ; Antigens, Differentiation, Myelomonocytic/*genetics ; Cell Adhesion Molecules/*genetics ; *Cloning, Molecular ; DNA/analysis ; Endothelium, Vascular/analysis/immunology ; Epitopes/immunology ; *Genes, Immunoglobulin ; Humans ; Immunoblotting ; Immunoglobulins ; Immunosorbent Techniques ; Molecular Sequence Data ; Platelet Membrane Glycoproteins/immunology ; Protein Conformation ; Repetitive Sequences, Nucleic Acid ; Sequence Homology, Nucleic Acid ; Signal Transduction
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  • 6
    Publication Date: 1990-12-07
    Description: The binding of a 13C-labeled cyclosporin A (CsA) analog to cyclophilin (peptidyl prolyl isomerase) was examined by means of isotope-edited nuclear magnetic resonance (NMR) techniques. A trans 9,10 peptide bond was adopted when CsA was bound to cyclophilin, in contrast to the cis 9,10 peptide bond found in the crystalline and solution conformations of CsA. Furthermore, nuclear Overhauser effects (NOEs) were observed between the zeta 3 and epsilon 3 protons of the methylleucine (MeLeu) residue at position 9 of CsA and tryptophan121 (Trp121) and phenylalanine (Phe) protons of cyclophilin, suggesting that the MeLeu9 residue of CsA interacts with cyclophilin. These results illustrate the power of isotope-edited NMR techniques for rapidly providing useful information about the conformations and active site environment of inhibitors bound to their target enzymes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fesik, S W -- Gampe, R T Jr -- Holzman, T F -- Egan, D A -- Edalji, R -- Luly, J R -- Simmer, R -- Helfrich, R -- Kishore, V -- Rich, D H -- New York, N.Y. -- Science. 1990 Dec 7;250(4986):1406-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2255910" target="_blank"〉PubMed〈/a〉
    Keywords: Amides ; Amino Acid Isomerases/chemistry/*metabolism ; Carbon Isotopes ; Carrier Proteins/chemistry/*metabolism ; Cyclosporins/chemistry/*metabolism ; Escherichia coli/genetics ; Humans ; Leucine/analogs & derivatives/chemistry ; Magnetic Resonance Spectroscopy/methods ; Peptidylprolyl Isomerase ; Phenylalanine/chemistry ; Protein Binding ; Protein Conformation ; Recombinant Proteins/chemistry/metabolism ; Tryptophan/chemistry
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  • 7
    Publication Date: 1990-07-27
    Description: The major autophosphorylation sites of the rat beta II isozyme of protein kinase C were identified. The modified threonine and serine residues were found in the amino-terminal peptide, the carboxyl-terminal tail, and the hinge region between the regulatory lipid-binding domain and the catalytic kinase domain. Because this autophosphorylation follows an intrapeptide mechanism, extraordinary flexibility of the protein is necessary to phosphorylate the three regions. Comparison of the sequences surrounding the modified residues showed no obvious recognition motif nor any similarity to substrate phosphorylation sites, suggesting that proximity to the active site may be the primary criterion for their phosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flint, A J -- Paladini, R D -- Koshland, D E Jr -- DK09765/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1990 Jul 27;249(4967):408-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2377895" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Brain/enzymology ; Cloning, Molecular ; Isoenzymes/genetics/*metabolism ; Molecular Sequence Data ; Peptide Fragments/isolation & purification/metabolism ; Phosphorylation ; Protein Conformation ; Protein Kinase C/genetics/*metabolism ; Rats ; Recombinant Proteins/metabolism ; Signal Transduction ; Trypsin
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-07-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carter, D C -- He, X M -- New York, N.Y. -- Science. 1990 Jul 20;249(4966):302-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Space Science Laboratory, NASA Marshall Space Flight Center, Huntsville, AL 35812.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2374930" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Models, Molecular ; Protein Conformation ; *Serum Albumin ; X-Ray Diffraction
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  • 9
    Publication Date: 1990-11-30
    Description: Conducting gramicidin channels form predominantly by the transmembrane association of monomers, one from each side of a lipid bilayer. In single-channel experiments in planar bilayers the two gramicidin analogs, [Val1]gramicidin A (gA) and [4,4,4-F3-Val1]gramicidin A (F3gA), form dimeric channels that are structurally equivalent and have characteristically different conductances. When these gramicidins were added asymmetrically, one to each side of a preformed bilayer, the predominant channel type was the hybrid channel, formed between two chemically dissimilar monomers. These channels formed by the association of monomers residing in each half of the membrane. These results also indicate that the hydrophobic gramicidins are surprisingly membrane impermeant, a conclusion that was confirmed in experiments in which gA was added asymmetrically and symmetrically to preformed bilayers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connell, A M -- Koeppe, R E 2nd -- Andersen, O S -- GM21342/GM/NIGMS NIH HHS/ -- GM34968/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 30;250(4985):1256-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, Cornell University Medical College, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1700867" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Membrane Permeability ; Chemistry, Physical ; Electric Conductivity ; Gramicidin/*chemistry/metabolism ; Ion Channels/*chemistry/physiology ; Kinetics ; Lipid Bilayers/*chemistry ; Macromolecular Substances ; Molecular Sequence Data ; Physicochemical Phenomena ; Protein Conformation
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-17
    Description: A class of transcriptional regulator proteins bind to DNA at dyad-symmetric sites through a motif consisting of (i) a "leucine zipper" sequence that associates into noncovalent, parallel, alpha-helical dimers and (ii) a covalently connected basic region necessary for binding DNA. The basic regions are predicted to be disordered in the absence of DNA and to form alpha helices when bound to DNA. These helices bind in the major groove forming multiple hydrogen-bonded and van der Waals contacts with the nucleotide bases. To test this model, two peptides were designed that were identical to natural leucine zipper proteins only at positions hypothesized to be critical for dimerization and DNA recognition. The peptides form dimers that bind specifically to DNA with their basic regions in alpha-helical conformations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Neil, K T -- Hoess, R H -- DeGrado, W F -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):774-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Central Research and Development Department, E.I. du Pont de Nemours & Co., Wilmington, DE 19880-0328.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2389143" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Chemistry, Physical ; Circular Dichroism ; Computer Simulation ; DNA/*metabolism ; DNA-Binding Proteins/*metabolism ; Hydrogen Bonding ; *Leucine ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Physicochemical Phenomena ; Protein Conformation
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  • 11
    Publication Date: 1990-12-07
    Description: A genetic system was developed in Escherichia coli to study leucine zippers with the amino-terminal domain of bacteriophage lambda repressor as a reporter for dimerization. This system was used to analyze the importance of the amino acid side chains at eight positions that form the hydrophobic interface of the leucine zipper dimer from the yeast transcriptional activator, GCN4. When single amino acid substitutions were analyzed, most functional variants contained hydrophobic residues at the dimer interface, while most nonfunctional sequence variants contained strongly polar or helix-breaking residues. In multiple randomization experiments, however, many combinations of hydrophobic residues were found to be nonfunctional, and leucines in the heptad repeat were shown to have a special function in leucine zipper dimerization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, J C -- O'Shea, E K -- Kim, P S -- Sauer, R T -- AI15706/AI/NIAID NIH HHS/ -- GM11117/GM/NIGMS NIH HHS/ -- GM44162/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 7;250(4986):1400-3.〈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/2147779" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacteriophage lambda/*genetics ; DNA-Binding Proteins/*genetics ; Escherichia coli/*genetics ; Fungal Proteins/*genetics ; Genetic Variation ; Leucine Zippers/*genetics ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Phenotype ; Protein Conformation ; *Protein Kinases ; Random Allocation ; Recombinant Fusion Proteins/metabolism ; *Saccharomyces cerevisiae Proteins ; Transcription Factors/*genetics
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  • 12
    Publication Date: 1990-07-27
    Description: The enzymatic degradation of cellulose is an important process, both ecologically and commercially. The three-dimensional structure of a cellulase, the enzymatic core of CBHII from the fungus Trichoderma reesei reveals an alpha-beta protein with a fold similar to but different from the widely occurring barrel topology first observed in triose phosphate isomerase. The active site of CBHII is located at the carboxyl-terminal end of a parallel beta barrel, in an enclosed tunnel through which the cellulose threads. Two aspartic acid residues, located in the center of the tunnel are the probable catalytic residues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rouvinen, J -- Bergfors, T -- Teeri, T -- Knowles, J K -- Jones, T A -- New York, N.Y. -- Science. 1990 Jul 27;249(4967):380-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, BMC, Uppsala, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2377893" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Cellulose/metabolism ; Cellulose 1,4-beta-Cellobiosidase ; Chemistry, Physical ; Crystallization ; Crystallography ; *Glycoside Hydrolases/metabolism ; Glycosylation ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Mitosporic Fungi/*enzymology ; Molecular Sequence Data ; Molecular Structure ; Physicochemical Phenomena ; Protein Conformation ; Trichoderma/*enzymology
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-09-28
    Description: To understand why proteins adopt particular three-dimensional structures, it is important to elucidate the hierarchy of interactions that stabilize the native state. Proteins in partly folded states can be used to dissect protein organizational hierarchies. A partly folded apomyoglobin intermediate has now been characterized structurally by trapping slowly exchanging peptide NH protons and analyzing them by two-dimensional 1H-NMR (nuclear magnetic resonance). Protons in the A, G, and H helix regions are protected from exchange, while protons in the B and E helix regions exchange freely. On the basis of these results and the three-dimensional structure of native myoglobin, a structural model is presented for the partly folded intermediate in which a compact subdomain retains structure while the remainder of the protein is essentially unfolded.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hughson, F M -- Wright, P E -- Baldwin, R L -- DK34909/DK/NIDDK NIH HHS/ -- GM19988/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 28;249(4976):1544-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Beckman Center, Stanford University School of Medicine, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2218495" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Apoproteins/chemistry/*metabolism ; Hydrogen-Ion Concentration ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Myoglobin/chemistry/*metabolism ; Protein Conformation ; Spectrophotometry, Ultraviolet
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  • 14
    Publication Date: 1990-08-31
    Description: The isocitrate dehydrogenase of Escherichia coli is an example of a ubiquitous class of enzymes that are regulated by covalent modification. In the three-dimensional structure of the enzyme-substrate complex, isocitrate forms a hydrogen bond with Ser113, the site of regulatory phosphorylation. The structures of Asp113 and Glu113 mutants, which mimic the inactivation of the enzyme by phosphorylation, show minimal conformational changes from wild type, as in the phosphorylated enzyme. Calculations based on observed structures suggest that the change in electrostatic potential when a negative charge is introduced either by phosporylation or site-directed mutagenesis is sufficient to inactivate the enzyme. Thus, direct interaction at a ligand binding site is an alternative mechanism to induced conformational changes from an allosteric site in the regulation of protein activity by phosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hurley, J H -- Dean, A M -- Sohl, J L -- Koshland, D E Jr -- Stroud, R M -- GM 24485/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 31;249(4972):1012-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2204109" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Escherichia coli/*enzymology/genetics ; Homeostasis ; Isocitrate Dehydrogenase/genetics/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Phosphorylation ; Protein Conformation
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  • 15
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Waldrop, M M -- New York, N.Y. -- Science. 1990 Aug 3;249(4968):472-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2382127" target="_blank"〉PubMed〈/a〉
    Keywords: Chemical Phenomena ; Chemistry ; *Information Systems ; Jurisprudence ; Societies, Scientific ; United States
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  • 16
    Publication Date: 1990-08-03
    Description: Comparison of the 2.4 angstrom resolution crystal structures of dimeric clam hemoglobin in the deoxygenated and carbon-monoxide liganded states shows how radically different the structural basis for cooperative oxygen binding is from that operative in mammalian hemoglobins. Heme groups are in direct communication across a novel subunit interface formed by the E and F helices. The conformational changes at this interface that accompany ligand binding are more dramatic at a tertiary level but more subtle at a quaternary level than those in mammalian hemoglobins. These findings suggest a cooperative mechanism that links ligation at one subunit with potentiation of affinity at the second subunit.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Royer, W E Jr -- Hendrickson, W A -- Chiancone, E -- New York, N.Y. -- Science. 1990 Aug 3;249(4968):518-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2382132" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Carboxyhemoglobin/metabolism ; Hemoglobins/*metabolism ; Ligands ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Mollusca ; Protein Conformation
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  • 17
    Publication Date: 1990-03-09
    Description: Comparison of a lambda repressor-operator complex and a 434 repressor-operator complex reveals that three conserved residues in the helix-turn-helix (HTH) region make similar contacts in each of the crystallographically determined structures. These conserved residues and their interactions with phosphodiester oxygens help establish a frame of reference within which other HTH residues make contacts that are critical for site-specific recognition. Such "positioning contacts" may be important conserved features within families of HTH proteins. In contrast, the structural comparisons appear to rule out any simple "recognition code" at the level of detailed side chain-base pair interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pabo, C O -- Aggarwal, A K -- Jordan, S R -- Beamer, L J -- Obeysekare, U R -- Harrison, S C -- GM 29109/GM/NIGMS NIH HHS/ -- GM 31471/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Mar 9;247(4947):1210-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2315694" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Asparagine ; Base Composition ; Base Sequence ; Binding Sites ; *DNA-Binding Proteins ; Glutamine ; Hydrogen Bonding ; Molecular Sequence Data ; Molecular Structure ; *Operator Regions, Genetic ; Protein Conformation ; Repressor Proteins/*metabolism ; Transcription Factors/*metabolism ; Viral Proteins ; Viral Regulatory and Accessory Proteins
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  • 18
    Publication Date: 1990-07-20
    Description: The crystallographic structure of a recombinant hirudin-thrombin complex has been solved at 2.3 angstrom (A) resolution. Hirudin consists of an NH2-terminal globular domain and a long (39 A) COOH-terminal extended domain. Residues Ile1 to Tyr3 of hirudin form a parallel beta-strand with Ser214 to Glu217 of thrombin with the nitrogen atom of Ile1 making a hydrogen bond with Ser195 O gamma atom of the catalytic site, but the specificity pocket of thrombin is not involved in the interaction. The COOH-terminal segment makes numerous electrostatic interactions with an anion-binding exosite of thrombin, whereas the last five residues are in a helical loop that forms many hydrophobic contacts. In all, 27 of the 65 residues of hirudin have contacts less than 4.0 A with thrombin (10 ion pairs and 23 hydrogen bonds). Such abundant interactions may account for the high affinity and specificity of hirudin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rydel, T J -- Ravichandran, K G -- Tulinsky, A -- Bode, W -- Huber, R -- Roitsch, C -- Fenton, J W 2nd -- HL13160/HL/NHLBI NIH HHS/ -- HL43229/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Jul 20;249(4966):277-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Michigan State University, East Lansing 48824.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2374926" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Hirudins/*metabolism ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Conformation ; Recombinant Proteins/metabolism ; Thrombin/*metabolism ; X-Ray Diffraction
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  • 19
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-10
    Description: A metalloantibody has been constructed with a coordination site for metals in the antigen binding pocket. The Zn(II) binding site from carbonic anhydrase B was used as a model. Three histidine residues have been placed in the light chain complementarity determining regions of a single chain antibody molecule. In contrast to the native protein, the mutant displayed metal-dependent fluorescence-quenching behavior. This response was interpreted as evidence for metal binding in the three-histidine site with relative affinities in the order Cu(II) greater than Zn(II) greater than Cd(II). The presence of metal cofactors in immunoglobulins should facilitate antibody catalysis of redox and hydrolytic reactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iverson, B L -- Iverson, S A -- Roberts, V A -- Getzoff, E D -- Tainer, J A -- Benkovic, S J -- Lerner, R A -- F32GM-1204702/GM/NIGMS NIH HHS/ -- IGM 37684/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 10;249(4969):659-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2116666" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Binding Sites, Antibody ; Cadmium ; Carbonic Anhydrases/*immunology ; Copper ; Fluoresceins ; Immunoglobulin Heavy Chains ; Immunoglobulin Light Chains ; Ligands ; *Metals ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Spectrometry, Fluorescence ; Zinc
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-02-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alper, J -- New York, N.Y. -- Science. 1990 Feb 16;247(4944):804-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2154848" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/drug therapy ; *Antiviral Agents/therapeutic use ; Capsid/ultrastructure ; Common Cold/*drug therapy ; Drug Design ; Humans ; Models, Molecular ; Protein Conformation ; Rhinovirus/ultrastructure ; Software
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  • 21
    Publication Date: 1990-04-27
    Description: Affinity-purified, polyclonal antibodies to the gamma subunit of the dihydropyridine (DHP)-sensitive, voltage-dependent calcium channel have been used to isolate complementary DNAs to the rabbit skeletal muscle protein from an expression library. The deduced primary structure indicates that the gamma subunit is a 25,058-dalton protein that contains four transmembrane domains and two N-linked glycosylation sites, consistent with biochemical analyses showing that the gamma subunit is a glycosylated hydrophobic protein. Nucleic acid hybridization studies indicate that there is a 1200-nucleotide transcript in skeletal muscle but not in brain or heart. The gamma subunit may play a role in assembly, modulation, or the structure of the skeletal muscle calcium channel.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jay, S D -- Ellis, S B -- McCue, A F -- Williams, M E -- Vedvick, T S -- Harpold, M M -- Campbell, K P -- HL-14388/HL/NHLBI NIH HHS/ -- HL-37187/HL/NHLBI NIH HHS/ -- HL-39265/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Apr 27;248(4954):490-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2158672" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Calcium Channels/drug effects/physiology ; DNA/isolation & purification ; Dihydropyridines/*pharmacology ; Disulfides ; Electrophoresis, Polyacrylamide Gel ; Immunoassay ; Macromolecular Substances ; Molecular Sequence Data ; Molecular Weight ; Muscles/*analysis ; Nucleic Acid Hybridization ; Protein Conformation ; RNA, Messenger/analysis ; Rabbits ; Sequence Homology, Nucleic Acid
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  • 22
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-12-07
    Description: The mammalian olfactory system may transduce odorant information via a G protein-mediated adenosine 3',5'-monophosphate (cAMP) cascade. A newly discovered adenylyl cyclase, termed type III, has been cloned, and its expression was localized to olfactory neurons. The type III protein resides in the sensory neuronal cilia, which project into the nasal lumen and are accessible to airborne odorants. The enzymatic activity of the type III adenylyl cyclase appears to differ from nonsensory cyclases. The large difference seen between basal and stimulated activity for the type III enzyme could allow considerable modulation of the intracellular cAMP concentration. This property may represent one mechanism of achieving sensitivity in odorant perception.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bakalyar, H A -- Reed, R R -- 5T32CA09339/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 7;250(4986):1403-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2255909" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/genetics/*physiology ; Amino Acid Sequence ; Animals ; Brain/enzymology/physiology ; Cell Line ; Clone Cells ; Cloning, Molecular ; Gene Library ; Glycosylation ; Isoenzymes/genetics/*physiology ; Macromolecular Substances ; Molecular Sequence Data ; Molecular Weight ; Neurons, Afferent/enzymology/physiology ; Nose/enzymology/physiology ; *Odors ; Protein Conformation ; Rats ; *Signal Transduction
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  • 23
    Publication Date: 1990-06-01
    Description: Transmembrane proteins serve important biological functions, yet precise information on their secondary and tertiary structure is very limited. The boundaries and structures of membrane-embedded domains in integral membrane proteins can be determined by a method based on a combination of site-specific mutagenesis and nitroxide spin labeling. The application to one polypeptide segment in bacteriorhodopsin, a transmembrane chromoprotein that functions as a light-driven proton pump is described. Single cysteine residues were introduced at 18 consecutive positions (residues 125 to 142). Each mutant was reacted with a specific spin label and reconstituted into vesicles that were shown to be functional. The relative collision frequency of each spin label with freely diffusing oxygen and membrane-impermeant chromium oxalate was estimated with power saturation EPR (electron paramagnetic resonance) spectroscopy. The results indicate that residues 129 to 131 form a short water-exposed loop, while residues 132 to 142 are membrane-embedded. The oxygen accessibility for positions 131 to 138 varies with a periodicity of 3.6 residues, thereby providing a striking demonstration of an alpha helix. The orientation of this helical segment with respect to the remainder of the protein was determined.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Altenbach, C -- Marti, T -- Khorana, H G -- Hubbell, W L -- AI 11479/AI/NIAID NIH HHS/ -- EY05216/EY/NEI NIH HHS/ -- GM28289/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Jun 1;248(4959):1088-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jules Stein Eye Institute, University of California, Los Angeles 90024-7008.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2160734" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Bacteriorhodopsins/genetics ; Cysteine/genetics ; Electron Spin Resonance Spectroscopy ; *Membrane Proteins/genetics ; Molecular Sequence Data ; Mutation ; Oxalates ; Oxalic Acid ; Oxygen ; Protein Conformation ; Spin Labels
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  • 24
    Publication Date: 1990-08-13
    Description: The three-dimensional structure of charybdotoxin, a high-affinity peptide blocker of several potassium ion channels, was determined by two-dimensional nuclear magnetic resonance (2-D NMR) spectroscopy. Unambiguous NMR assignments of backbone and side chain hydrogens were made for all 37 amino acids. The structure was determined by distance geometry and refined by nuclear Overhauser and exchange spectroscopy back calculation. The peptide is built on a foundation of three antiparallel beta strands to which other parts of the sequence are attached by three disulfide bridges. The overall shape is roughly ellipsoidal, with axes of approximately 2.5 and 1.5 nanometers. Nine of the ten charged groups are located on one side of the ellipsoid, with seven of the eight positive residues lying in a stripe 2.5 nanometers in length. The other side displays three hydrophobic residues projecting prominently into aqueous solution. The structure rationalizes several mechanistic features of charybdotoxin block of the high-conductance Ca2(+)-activated K+ channel.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Massefski, W Jr -- Redfield, A G -- Hare, D R -- Miller, C -- GM-20168/GM/NIGMS NIH HHS/ -- GM-31768/GM/NIGMS NIH HHS/ -- RR0031/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 3;249(4968):521-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Department of Biochemistry, Brandeis University, Waltham, MA 02254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1696395" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Charybdotoxin ; Disulfides/analysis ; Magnetic Resonance Spectroscopy/methods ; Models, Molecular ; Molecular Sequence Data ; Potassium Channels/drug effects ; Protein Conformation ; *Scorpion Venoms/pharmacology
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  • 25
    Publication Date: 1990-12-21
    Description: Human growth hormone (hGH) elicits a diverse set of biological activities including lactation that derives from binding to the prolactin (PRL) receptor. The binding affinity of hGH for the extracellular binding domain of the hPRL receptor (hPRLbp) was increased about 8000-fold by addition of 50 micromolar ZnCl2. Zinc was not required for binding of hGH to the hGH binding protein (hGHbp) or for binding of hPRL to the hPRLbp. Other divalent metal ions (Ca2+, Mg2+, Cu2+, Mn2+, and Co2+) at physiological concentrations did not support such strong binding. Scatchard analysis indicated a stoichiometry of one Zn2+ per hGH.hPRLbp complex. Mutational analysis showed that a cluster of three residues (His18, His21, and Glu174) in hGH and His188 from the hPRLbp (conserved in all PRL receptors but not GH receptors) are probable Zn2+ ligands. This polypeptide hormone.receptor "zinc sandwich" provides a molecular mechanism to explain why nonprimate GHs are not lactogenic and offers a molecular link between zinc deficiency and its association with altered functions of hGH.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cunningham, B C -- Bass, S -- Fuh, G -- Wells, J A -- New York, N.Y. -- Science. 1990 Dec 21;250(4988):1709-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2270485" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Chlorides/*pharmacology ; Growth Hormone/*metabolism ; Humans ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligonucleotide Probes ; Plasmids ; Protein Conformation ; Receptors, Prolactin/drug effects/genetics/*metabolism ; Restriction Mapping ; Zinc/metabolism/*pharmacology ; *Zinc Compounds
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  • 26
    Publication Date: 1990-05-11
    Description: The three-dimensional structures of an antibody to a peptide and its complex with the peptide antigen have been determined at 2.8 A resolution. The antigen is a synthetic 19-amino acid peptide homolog of the C helix of myohemerythrin (Mhr). The unliganded Fab' crystals are orthorhombic with two molecules per asymmetric unit, whereas the complex crystals are hexagonal with one molecule per asymmetric unit. The Fab' and the Fab'-peptide complex structures have been solved independently by molecular replacement methods and have crystallographic R factors of 0.197 and 0.215, respectively, with no water molecules included. The amino-terminal portion of the peptide sequence (NH2-Glu-Val-Val-Pro-His-Lys-Lys) is clearly interpretable in the electron density map of the Fab'-peptide complex and adopts a well-defined type II beta-turn in the concave antigen binding pocket. This same peptide amino acid sequence in native Mhr is alpha-helical. The peptide conformation when bound to the Fab' is inconsistent with binding of the Fab' to native Mhr, and suggests that binding of the Fab' to conformationally altered forms of the native Mhr or to apo-Mhr. Immunological mapping previously identified this sequence as the peptide epitope, and its fine specificity correlates well with the structural analysis. The binding pocket includes a large percentage of hydrophobic residues. The buried surfaces of the peptide and the antibody are complementary in shape and cover 460 A2 and 540 A2, respectively. These two structures now enable a comparison of a specific monoclonal Fab' both in its free and antigen complexed state. While no major changes in the antibody were observed when peptide was bound, there were some small but significant side chain and main chain rearrangements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stanfield, R L -- Fieser, T M -- Lerner, R A -- Wilson, I A -- AI-07244/AI/NIAID NIH HHS/ -- GM38794/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 May 11;248(4956):712-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, California 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2333521" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Antigen-Antibody Complex ; Crystallization ; *Hemerythrin/analogs & derivatives/immunology ; *Immunoglobulin Fab Fragments ; *Metalloproteins/immunology ; *Models, Molecular ; Molecular Sequence Data ; Peptides/*immunology ; Pigments, Biological ; Protein Conformation ; Software ; X-Ray Diffraction
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  • 27
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-01-05
    Description: It has been proposed that dithiol-disulfide interchange and oxidation-reduction reactions may play a role in hormone-induced receptor activation. Inspection of the sequences of the gonadotropic hormones revealed a homologous tetrapeptide (Cys-Gly-Pro-Cys) between the beta subunit of lutropin (LH) and the active site of thioredoxin (TD). The beta subunit of follitropin (FSH) has a similar sequence (Cys-Gly-Lys-Cys). Thioredoxin is a ubiquitous protein serving as an electron donor for ribonucleotide reductase, but it also exhibits disulfide isomerase activity. The catalytic activity of TD was assayed by its ability to reactivate reduced and denatured ribonuclease. In this assay, the purified ovine FSH and bovine LH preparations tested were approximately 60 and approximately 300 times, respectively, as active as TD on a molar basis. This heretofore unsuspected catalytic property of FSH and LH may be important in understanding their mechanism of receptor activation and signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boniface, J J -- Reichert, L E Jr -- HD-13938/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1990 Jan 5;247(4938):61-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Albany Medical College, NY 12208.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2104678" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bacterial Proteins/*metabolism ; Follicle Stimulating Hormone/*metabolism ; Humans ; Luteinizing Hormone/*metabolism ; Molecular Sequence Data ; Oxidation-Reduction ; Protein Conformation ; Receptors, FSH/metabolism ; Receptors, LH/metabolism ; Ribonucleases/metabolism ; Signal Transduction ; Thioredoxins/*metabolism
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-17
    Description: A recently described class of DNA binding proteins is characterized by the "bZIP" motif, which consists of a basic region that contacts DNA and an adjacent "leucine zipper" that mediates protein dimerization. A peptide model for the basic region of the yeast transcriptional activator GCN4 has been developed in which the leucine zipper has been replaced by a disulfide bond. The 34-residue peptide dimer, but not the reduced monomer, binds DNA with nanomolar affinity at 4 degrees C. DNA binding is sequence-specific as judged by deoxyribonuclease I footprinting. Circular dichroism spectroscopy suggests that the peptide adopts a helical structure when bound to DNA. These results demonstrate directly that the GCN4 basic region is sufficient for sequence-specific DNA binding and suggest that a major function of the GCN4 leucine zipper is simply to mediate protein dimerization. Our approach provides a strategy for the design of short sequence-specific DNA binding peptides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Talanian, R V -- McKnight, C J -- Kim, P S -- GM13665/GM/NIGMS NIH HHS/ -- GM44162/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):769-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Nine Cambridge Center, MA 02142.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2389142" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Circular Dichroism ; DNA/*metabolism ; DNA-Binding Proteins/*metabolism ; Deoxyribonuclease I ; Disulfides ; Fungal Proteins/*metabolism ; Leucine ; Macromolecular Substances ; Molecular Sequence Data ; Peptides/*metabolism ; Protein Conformation ; *Protein Kinases ; *Saccharomyces cerevisiae Proteins ; Transcription Factors/*metabolism
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  • 29
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-03-09
    Description: Under stationary conditions, opening and closing of single Torpedo electroplax chloride channels show that the number of transitions per unit time between inactivated and conducting states are unequal in opposite directions. This asymmetry, which increases with transmembrane electrochemical gradient for the chloride ion, violates the principle of microscopic reversibility and thus demonstrates that the channel-gating process is not at thermodynamic equilibrium. The results imply that the channel's conformational states are coupled to the transmembrane electrochemical gradient of the chloride ion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richard, E A -- Miller, C -- GM-31768/GM/NIGMS NIH HHS/ -- NS-07292/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Mar 9;247(4947):1208-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Graduate Department of Biochemistry, Brandeis University, Waltham, MA 02254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2156338" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/*physiology ; Chloride Channels ; Chlorides/metabolism/*physiology ; Electric Conductivity ; Electric Organ/*physiology ; Electrochemistry ; Membrane Potentials ; Membrane Proteins/*physiology ; Models, Biological ; Protein Conformation ; Thermodynamics ; Torpedo/*physiology
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-08-31
    Description: The sodium- and potassium-dependent adenosine triphosphatase (Na+,K(+)-ATPase) maintains the transmembrane Na+ gradient to which is coupled all active cellular transport systems. The R and S alleles of the gene encoding the Na+,K(+)-ATPase alpha 1 subunit isoform were identified in Dahl salt-resistant (DR) and Dahl salt-sensitive (DS) rats, respectively. Characterization of the S allele-specific Na+,K(+)-ATPase alpha 1 complementary DNA identified a leucine substitution of glutamine at position 276. This mutation alters the hydropathy profile of a region in proximity to T3(Na), the trypsin-sensitive site that is only detected in the presence of Na+. This mutation causes a decrease in the rubidium-86 influx of S allele-specific sodium pumps, thus marking a domain in the Na+,K(+)-ATPase alpha subunit important for K+ transport, and supporting the hypothesis of a putative role of these pumps in hypertension.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herrera, V L -- Ruiz-Opazo, N -- HL 01967/HL/NHLBI NIH HHS/ -- HL 18318/HL/NHLBI NIH HHS/ -- HL 39267/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 31;249(4972):1023-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, MA 02118.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1975705" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Membrane/enzymology ; Kidney/enzymology ; Kinetics ; Molecular Sequence Data ; *Mutation ; Polymorphism, Restriction Fragment Length ; Protein Conformation ; Rats ; Rats, Inbred Strains ; Rubidium/*metabolism ; Rubidium Radioisotopes ; Sodium-Potassium-Exchanging ATPase/*genetics/metabolism
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  • 31
    Publication Date: 1990-10-05
    Description: Rhodopsin is a member of a family of receptors that contain seven transmembrane helices and are coupled to G proteins. The nature of the interactions between rhodopsin mutants and the G protein, transduction (Gt), was investigated by flash photolysis in order to monitor directly Gt binding and dissociation. Three mutant opsins with alterations in their cytoplasmic loops bound 11-cis-retinal to yield pigments with native rhodopsin absorption spectra, but they failed to stimulate the guanosine triphosphatase activity of Gt. The opsin mutations included reversal of a charged pair conserved in all G protein-coupled receptors at the cytoplasmic border of the third transmembrane helix (mutant CD1), replacement of 13 amino acids in the second cytoplasmic loop (mutant CD2), and deletion of 13 amino acids from the third cytoplasmic loop (mutant EF1). Whereas mutant CD1 failed to bind Gt, mutants CD2 and EF1 showed normal Gt binding but failed to release Gt in the presence of guanosine triphosphate. Therefore, it appears that at least the second and third cytoplasmic loops of rhodopsin are required for activation of bound Gt.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Franke, R R -- Konig, B -- Sakmar, T P -- Khorana, H G -- Hofmann, K P -- New York, N.Y. -- Science. 1990 Oct 5;250(4977):123-5.〈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/2218504" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cell Membrane/metabolism ; Chromosome Deletion ; Micelles ; Models, Molecular ; Molecular Sequence Data ; *Mutation ; Photolysis ; Protein Binding ; Protein Conformation ; Rhodopsin/genetics/*metabolism ; Transducin/*metabolism ; Transfection
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  • 32
    Publication Date: 1990-02-16
    Description: A region in the human immunodeficiency virus (HIV) env message, with the potential to form a complex secondary structure (designated RRE), interacts with the rev protein (Rev). This interaction is believed to mediate export of HIV structural messenger RNAs from the nucleus to the cytoplasm. In this report the regions essential for Rev interaction with the RRE are further characterized and the functional significance of Rev-RRE interaction in vivo is examined. A single hairpin loop structure within the RRE was found to be a primary determinant for Rev binding in vitro and Rev response in vivo. Maintenance of secondary structure, rather than primary nucleotide sequence alone, appeared to be necessary for Rev-RNA interaction, which distinguishes it from the mechanism for cis-acting elements in DNA. Limited changes within the 200 nucleotides, which preserved the proper RRE conformational structure, were well tolerated for Rev binding and function. Thus, variation among the RRE elements present in the diverse HIV isolates would have little, if any, effect on Rev responsiveness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olsen, H S -- Nelbock, P -- Cochrane, A W -- Rosen, C A -- New York, N.Y. -- Science. 1990 Feb 16;247(4944):845-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Oncology and Virology, Roche Institute of Molecular Biology, Nutley, NJ 07110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2406903" target="_blank"〉PubMed〈/a〉
    Keywords: Base Composition ; Base Sequence ; Chromosome Deletion ; Gene Products, rev/genetics/*metabolism ; Genes, rev ; HIV/*genetics/metabolism ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Plasmids ; Protein Conformation ; RNA, Messenger/*genetics/metabolism ; RNA, Viral/genetics/metabolism ; Trans-Activators/*metabolism ; rev Gene Products, Human Immunodeficiency Virus
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  • 33
    Publication Date: 1990-12-14
    Description: A chemical description of the action of phospholipase A2 (PLA2) can now be inferred with confidence from three high-resolution x-ray crystal structures. The first is the structure of the PLA2 from the venom of the Chinese cobra (Naja naja atra) in a complex with a phosphonate transition-state analogue. This enzyme is typical of a large, well-studied homologous family of PLA2S. The second is a similar complex with the evolutionarily distant bee-venom PLA2. The third structure is the uninhibited PLA2 from Chinese cobra venom. Despite the different molecular architectures of the cobra and bee-venom PLA2s, the transition-state analogue interacts in a nearly identical way with the catalytic machinery of both enzymes. The disposition of the fatty-acid side chains suggests a common access route of the substrate from its position in the lipid aggregate to its productive interaction with the active site. Comparison of the cobra-venom complex with the uninhibited enzyme indicates that optimal binding and catalysis at the lipid-water interface is due to facilitated substrate diffusion from the interfacial binding surface to the catalytic site rather than an allosteric change in the enzyme's structure. However, a second bound calcium ion changes its position upon the binding of the transition-state analogue, suggesting a mechanism for augmenting the critical electrophile.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443688/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443688/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scott, D L -- White, S P -- Otwinowski, Z -- Yuan, W -- Gelb, M H -- Sigler, P B -- GM22324/GM/NIGMS NIH HHS/ -- HL36235/HL/NHLBI NIH HHS/ -- R01 HL036235/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 14;250(4987):1541-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2274785" target="_blank"〉PubMed〈/a〉
    Keywords: Bee Venoms/analysis ; Binding Sites ; Calcium/metabolism ; Catalysis ; Chemistry, Physical ; Cobra Venoms/analysis ; Models, Molecular ; Molecular Structure ; Organophosphonates/metabolism ; Phospholipases A/chemistry/*metabolism ; Phospholipases A2 ; Phospholipids/metabolism ; Physicochemical Phenomena ; Protein Conformation ; X-Ray Diffraction
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  • 34
    Publication Date: 1990-12-14
    Description: The 2.0 angstroms crystal structure of a complex containing bee-venom phospholipase A2 (PLA2) and a phosphonate transition-state analogue was solved by multiple isomorphous replacement. The electron-density map is sufficiently detailed to visualize the proximal sugars of the enzyme's N-linked carbohydrate and a single molecule of the transition-state analogue bound ot its active center. Although bee-venom PLA2 does not belong to the large homologous Class I/II family that encompasses most other well-studied PLA2s, there is segmental sequence similarity and conservation of many functional substructures. Comparison of the bee-venom enzyme with other phospholipase structures provides compelling evidence for a common catalytic mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scott, D L -- Otwinowski, Z -- Gelb, M H -- Sigler, P B -- GM22324/GM/NIGMS NIH HHS/ -- HL36235/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 14;250(4987):1563-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2274788" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bee Venoms/*analysis ; Binding Sites ; Calcium/metabolism ; Carbohydrate Metabolism ; Catalysis ; Chemistry, Physical ; Crystallization ; Hydrogen Bonding ; Molecular Sequence Data ; Molecular Structure ; Phosphatidylethanolamines/*metabolism ; Phospholipases A/*chemistry/metabolism ; Phospholipases A2 ; Physicochemical Phenomena ; Protein Conformation
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  • 35
    Publication Date: 1990-07-20
    Description: Studies of the subunit interactions of the multicomponent T cell antigen receptor (TCR) revealed that specific pairs of chains have the ability to assemble after transfection into fibroblasts. For one such pair, TCR-alpha and CD3-delta, their ability to assemble was encoded by their transmembrane domains. The specificity of this interaction suggests that well-defined helical interactions in the membrane can explain the assembly of some multichain membrane complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manolios, N -- Bonifacino, J S -- Klausner, R D -- New York, N.Y. -- Science. 1990 Jul 20;249(4966):274-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2142801" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, CD3 ; Antigens, Differentiation, T-Lymphocyte/genetics ; Cell Line ; Cell Membrane/immunology ; Codon/genetics ; Macromolecular Substances ; Molecular Sequence Data ; Protein Conformation ; *Protein Processing, Post-Translational ; Receptors, Antigen, T-Cell/*genetics/metabolism ; Transfection
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  • 36
    Publication Date: 1990-03-16
    Description: An amino acid sequence encodes a message that determines the shape and function of a protein. This message is highly degenerate in that many different sequences can code for proteins with essentially the same structure and activity. Comparison of different sequences with similar messages can reveal key features of the code and improve understanding of how a protein folds and how it performs its function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bowie, J U -- Reidhaar-Olson, J F -- Lim, W A -- Sauer, R T -- AI-15706/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1990 Mar 16;247(4948):1306-10.〈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/2315699" target="_blank"〉PubMed〈/a〉
    Keywords: *Amino Acid Sequence ; Computer Graphics ; *DNA-Binding Proteins ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Proteins/*physiology/ultrastructure ; Repressor Proteins ; Structure-Activity Relationship ; Surface Properties ; Viral Proteins ; Viral Regulatory and Accessory Proteins
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  • 37
    Publication Date: 1990-12-21
    Description: lambda Cro is a dimeric DNA binding protein. Random mutagenesis and a selection for Cro activity have been used to identify the contacts between Cro subunits that are crucial for maintenance of a stably folded structure. To obtain equivalent contacts in a monomeric system, a Cro variant was designed and constructed in which the antiparallel beta-ribbon that forms the dimer interface was replaced by a beta-hairpin. The engineered monomer has a folded structure similar to wild type, is significantly more stable than wild type, and exhibits novel half-operator binding activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mossing, M C -- Sauer, R T -- AI-16982/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 21;250(4988):1712-5.〈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/2148648" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacteriophage lambda/*genetics ; Circular Dichroism ; *DNA-Binding Proteins ; Escherichia coli/genetics ; *Genetic Variation ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis ; Protein Conformation ; Repressor Proteins/*genetics/metabolism ; Thermodynamics ; Transcription Factors/*genetics ; Viral Proteins ; Viral Regulatory and Accessory Proteins
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  • 38
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-09-14
    Description: Direct osmotic stress measurements have been made of forces between helices of xanthan, an industrially important charged polysaccharide. Exponentially decaying hydration forces, much like those already measured between lipid bilayer membranes or DNA double helices, dominate the interactions at close separation. Interactions between uncharged schizophyllans also show the same kind of hydration force seen between xanthans. In addition to the practical possibilities for modifying solution and suspension properties through recognition and control of molecular forces, there is now finally the opportunity for theorists to relate macroscopic properties of a polymer solution to the microscopic properties that underlie them.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rau, D C -- Parsegian, V A -- New York, N.Y. -- Science. 1990 Sep 14;249(4974):1278-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases, National Institues of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2144663" target="_blank"〉PubMed〈/a〉
    Keywords: Carbohydrate Sequence ; Chemical Phenomena ; Chemistry ; Gels ; *Glycosaminoglycans ; Macromolecular Substances ; Molecular Sequence Data ; Osmosis ; *Polysaccharides, Bacterial ; *Sizofiran ; Solutions ; Viscosity
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-02-02
    Description: Protein unfolding and the dissolution of hydrophobic compounds (including solids, liquids, and gases) in water are characterized by a linear relation between entropy change and heat capacity change. The same slope is found for various classes of compounds, whereas the intercept depends on the particular class. The feature common to these processes is exposure of hydrophobic groups to water. These observations make possible the assignment of the heat capacity change to hydrophobic solvation and lead to the description of protein stability in terms of a hydrophobic and a nonhydrophobic contribution. A general representation of protein stability is given by the heat capacity change and the temperature.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murphy, K P -- Privalov, P L -- Gill, S J -- New York, N.Y. -- Science. 1990 Feb 2;247(4942):559-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2300815" target="_blank"〉PubMed〈/a〉
    Keywords: Chemical Phenomena ; Chemistry ; *Protein Denaturation ; *Proteins ; Thermodynamics
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  • 40
    Publication Date: 1990-07-13
    Description: The three-dimensional structure of the DNA-binding domain (DBD) of the glucocorticoid receptor has been determined by nuclear magnetic resonance spectroscopy and distance geometry. The structure of a 71-residue protein fragment containing two "zinc finger" domains is based on a large set of proton-proton distances derived from nuclear Overhauser enhancement spectra, hydrogen bonds in previously identified secondary structure elements, and coordination of two zinc atoms by conserved cysteine residues. The DBD is found to consist of a globular body from which the finger regions extend. A model of the dimeric complex between the DBD and the glucocorticoid response element is proposed. The model is consistent with previous results indicating that specific amino acid residues of the DBD are involved in protein-DNA and protein-protein interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hard, T -- Kellenbach, E -- Boelens, R -- Maler, B A -- Dahlman, K -- Freedman, L P -- Carlstedt-Duke, J -- Yamamoto, K R -- Gustafsson, J A -- Kaptein, R -- New York, N.Y. -- Science. 1990 Jul 13;249(4965):157-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2115209" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; DNA/*metabolism ; DNA-Binding Proteins/analysis/*metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Metalloproteins/analysis ; Models, Molecular ; Molecular Sequence Data ; Peptide Fragments/analysis/metabolism ; Protein Conformation ; Rats ; Receptors, Glucocorticoid/*analysis/metabolism ; Regulatory Sequences, Nucleic Acid ; Zinc/analysis
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-12-21
    Description: T lymphocyte activation requires recognition by the T cell of peptide fragments of foreign antigen bound to a self major histocompatibility complex (MHC) molecule. Genetic evidence suggests that part of the class II region of the MHC influences the expression, in trans, of MHC class I antigens on the cell surface, by regulating the availability of peptides that bind to and stabilize the class I molecule. Two closely related genes in this region, HAM1 and HAM2, were cloned and had sequence similarities to a superfamily of genes involved in the ATP-dependent transport of a variety of substrates across cell membranes. Thus, these MHC-linked transport protein genes may be involved in transporting antigen, or peptide fragments thereof, from the cytoplasm into a membrane-bounded compartment containing newly synthesized MHC molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monaco, J J -- Cho, S -- Attaya, M -- GM38774/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 21;250(4988):1723-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0678.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2270487" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Carrier Proteins/*genetics ; Cell Line ; Cloning, Molecular ; *Major Histocompatibility Complex ; Mice ; Molecular Sequence Data ; *Multigene Family ; Protein Conformation ; Sequence Homology, Nucleic Acid ; T-Lymphocytes/*immunology
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  • 42
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-06-22
    Description: A peptide having enzyme-like catalytic activity has been designed and synthesized. Computer modeling was used to design a bundle of four short parallel amphipathic helical peptides bearing the serine protease catalytic site residues serine, histidine, and aspartic acid at the amino end of the bundle in the same spatial arrangement as in chymotrypsin (ChTr). The necessary "oxyanion hole" and substrate binding pocket for acetyltyrosine ethyl ester, a classical ChTr substrate, were included in the design. The four chains were linked covalently at their carboxyl ends. The peptide has affinity for ChTr ester substrates similar to that of ChTr and hydrolyzes them at rates approximately 0.01 that of ChTr; total turnovers greater than 100 have been observed. The peptide is inhibited by ChTr specific inhibitors and is inactive toward benzoyl arginine ethyl ester, a trypsin substrate. The peptide is inactivated by heating above 60 degrees C, but recovers full catalytic activity upon cooling and lyophilization from acetic acid.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hahn, K W -- Klis, W A -- Stewart, J M -- BRS 888/RS/DRS NIH HHS/ -- New York, N.Y. -- Science. 1990 Jun 22;248(4962):1544-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Colorado Medical School, Denver 80262.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2360048" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Chromatography, High Pressure Liquid ; Chymotrypsin/antagonists & inhibitors/*chemical synthesis/metabolism ; Computer Simulation ; Esterases/antagonists & inhibitors/*chemical synthesis/metabolism ; Hot Temperature ; Hydrogen-Ion Concentration ; Hydrolysis ; Models, Chemical ; Molecular Sequence Data ; Peptides/antagonists & inhibitors/*chemical synthesis/metabolism ; Protein Conformation ; Substrate Specificity ; Tyrosine/analogs & derivatives/metabolism
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  • 43
    Publication Date: 1990-08-24
    Description: The principal neutralizing determinant (PND) of human immunodeficiency virus HIV-1 is part of a disulfide bridged loop in the third variable region of the external envelope protein, gp120. Analysis of the amino acid sequences of this domain from 245 different HIV-1 isolates revealed that the PND is less variable than thought originally. Conservation to better than 80 percent of the amino acids in 9 out of 14 positions in the central portion of the PND and the occurrence of particular oligopeptide sequences in a majority of the isolates suggest that there are constraints on PND variability. One constraining influence may be the structural motif (beta strand--type II beta turn--beta strand--alpha helix) predicted for the consensus PND sequence by a neural network approach. Isolates with a PND similar to the commonly investigated human T cell lymphoma virus IIIB (HTLV-IIIB) and LAV-1 (BRU) strains were rare, and only 14 percent of sera from 86 randomly selected HIV-1 seropositive donors contained antibodies that recognized the PND of these virus isolates. In contrast, over 65 percent of these sera reacted with peptides containing more common PND sequences. These results suggest that HIV vaccine immunogens chosen because of their similarity to the consensus PND sequence and structure are likely to induce antibodies that neutralize a majority of HIV-1 isolates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉LaRosa, G J -- Davide, J P -- Weinhold, K -- Waterbury, J A -- Profy, A T -- Lewis, J A -- Langlois, A J -- Dreesman, G R -- Boswell, R N -- Shadduck, P -- New York, N.Y. -- Science. 1990 Aug 24;249(4971):932-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Repligen Corporation, Cambridge, MA 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2392685" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Genetic Variation ; HIV Envelope Protein gp120/*genetics ; *HIV Seropositivity ; HIV-1/*genetics/isolation & purification/pathogenicity ; Humans ; Military Personnel ; Molecular Sequence Data ; Protein Conformation ; United States
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-03-02
    Description: Ultrasound has become an important synthetic tool in liquid-solid chemical reactions, but the origins of the observed enhancements remained unknown. The effects of high-intensity ultrasound on solid-liquid slurries were examined. Turbulent flow and shock waves produced by acoustic cavitation were found to drive metal particles together at sufficiently high velocities to induce melting upon collision. A series of transition-metal powders were used to probe the maximum temperatures and speeds reached during such interparticle collisions. Metal particles that were irradiated in hydrocarbon liquids with ultrasound underwent collisions at roughly half the speed of sound and generated localized effective temperatures between 2600 degrees C and 3400 degrees C at the point of impact for particles with an average diameter of approximately 10 microns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doktycz, S J -- Suslick, K S -- New York, N.Y. -- Science. 1990 Mar 2;247(4946):1067-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemical Sciences, University of Illinois, Urbana 61801.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2309118" target="_blank"〉PubMed〈/a〉
    Keywords: Chemical Phenomena ; Chemistry ; *Metals ; Microscopy, Electron, Scanning ; Microspheres ; *Ultrasonics
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-01-12
    Description: Experiments are presented that confirm earlier predictions that the mode of supply of reactants to a nonlinear (bio)chemical reaction determines or controls concentrations at steady states far from equilibrium. The oxidation of nicotinamide adenine dinucleotide (NADH) catalyzed by the enzyme horseradish peroxidase with continuous input of oxygen was studied; NAD+ is continuously recycled to NADH through a glucose-6-phosphate dehydrogenase system. A comparison of steady-state concentrations is made with an oscillatory oxygen input and a constant input at the same average oxygen input for both modes. By varying the frequency and amplitude of the perturbation (O2 influx), the following may be changed: the average concentration of NADH; the Gibbs free energy difference delta G of the reactants and products at steady state; the average rate of the reaction; the phase relation between the oscillatory rate and delta G; and the dissipation. These results confirm the possibility of an "alternating current chemistry," of control and optimization of thermodynamic efficiency and dissipation by means of external variation of constraints in classes of nonlinear reactions and biological pumps, and of improvements of the yield in such reactions (heterogeneous catalysis, for example).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lazar, J G -- Ross, J -- New York, N.Y. -- Science. 1990 Jan 12;247(4939):189-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Stanford University, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2294601" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Chemical Phenomena ; Chemistry ; Glucosephosphate Dehydrogenase/*metabolism ; Horseradish Peroxidase/*metabolism ; Kinetics ; NAD/*metabolism ; Oxidation-Reduction ; Oxygen/metabolism ; Peroxidases/*metabolism ; Thermodynamics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 46
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-01-26
    Description: A physical model in which cells are considered as possible detectors of very weak periodic electric fields yields a general relation between cell size and both thermally induced fluctuations in membrane potential and the maximum change in membrane potential caused by an applied field. The simplest version of the model provides a broad-band estimate of the smallest applied electric field to which membrane macromolecules can directly respond (about 10(-3) volt per centimeter). Much smaller fields (10(-6) volt per centimeter) can be detected if there is a response in only a narrow band of frequencies or if signal averaging occurs through field-induced variation in the catalytic activity of membrane-associated enzymes. Both extensions of the simplest version remove the apparent violation of the thermal noise limit found in some experiments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weaver, J C -- Astumian, R D -- New York, N.Y. -- Science. 1990 Jan 26;247(4941):459-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2300806" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Physiological Phenomena ; Cells/cytology ; Electric Conductivity ; *Electricity ; Enzymes/metabolism ; Membrane Potentials ; Membrane Proteins/metabolism ; Models, Biological ; Protein Conformation
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  • 47
    Publication Date: 1990-08-17
    Description: The interaction of a protein antigen, horse cytochrome c (cyt c), with a monoclonal antibody has been studied by hydrogen-deuterium (H-D) exchange labeling and two-dimensional nuclear magnetic resonance (2D NMR) methods. The H-exchange rate of residues in three discontiguous regions of the cyt c polypeptide backbone was slowed by factors up to 340-fold in the antibody-antigen complex compared with free cyt c. The protected residues, 36 to 38, 59, 60, 64 to 67, 100, and 101, and their hydrogen-bond acceptors, are brought together in the three-dimensional structure to form a contiguous, largely exposed protein surface with an area of about 750 square angstroms. The interaction site determined in this way is consistent with prior epitope mapping studies and includes several residues that were not previously identified. The hydrogen exchange labeling approach can be used to map binding sites on small proteins in antibody-antigen complexes and may be applicable to protein-protein and protein-ligand interactions in general.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432411/" 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/PMC3432411/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paterson, Y -- Englander, S W -- Roder, H -- GM 31847/GM/NIGMS NIH HHS/ -- GM 35926/GM/NIGMS NIH HHS/ -- R01 GM031847/GM/NIGMS NIH HHS/ -- S07-RR-05415-28/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 17;249(4970):755-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Pennsylvania, Philadelphia 19104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1697101" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal/immunology/metabolism ; Antigen-Antibody Complex ; *Binding Sites, Antibody ; Chemical Phenomena ; Chemistry ; Cytochrome c Group/*immunology ; Deuterium ; Epitopes/immunology ; Hydrogen/*metabolism ; Hydrogen Bonding ; Kinetics ; *Magnetic Resonance Spectroscopy ; Molecular Structure ; Protein Conformation
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 1990 Dec 21;250(4988):1657-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2270477" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Viral/immunology ; Histocompatibility Antigens Class I/genetics/*immunology ; Humans ; *Immunity, Cellular ; *Major Histocompatibility Complex ; Models, Molecular ; Protein Conformation
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  • 49
    Publication Date: 1990-12-14
    Description: The crystal structure of a complex between a phosphonate transition-state analogue and the phospholipase A2 (PLA2) from Naja naja atra venom has been solved and refined to a resolution of 2.0 angstroms. The identical stereochemistry of the two complexes that comprise the crystal's asymmetric unit indicates both the manner in which the transition state is stabilized and how the hydrophobic fatty acyl chains of the substrate are accommodated by the enzyme during interfacial catalysis. The critical features that suggest the chemistry of binding and catalysis are the same as those seen in the crystal structure of a similar complex formed with the evolutionarily distant bee-venom PLA2.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉White, S P -- Scott, D L -- Otwinowski, Z -- Gelb, M H -- Sigler, P B -- GM22324/GM/NIGMS NIH HHS/ -- HL 36235/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1990 Dec 14;250(4987):1560-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2274787" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bee Venoms/analysis ; Binding Sites ; Calcium/metabolism ; Catalysis ; Chemistry, Physical ; Cobra Venoms/*analysis ; Crystallization ; Hydrogen Bonding ; Molecular Sequence Data ; Molecular Structure ; Phosphatidylethanolamines/*metabolism ; Phospholipases A/*chemistry/metabolism ; Phospholipases A2 ; Physicochemical Phenomena ; Protein Conformation
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  • 50
    Publication Date: 1990-09-07
    Description: A protein crystal structure is usually described by one single structure, which largely omits the dynamical behavior of the molecule. A molecular dynamics method with a time-averaged crystallographic restraint was used to overcome this limitation. This method yields an ensemble of structures in which all possible thermal motions are allowed, that is, in additional to isotropic distributions, anisotropic and anharmonic positional distributions occur as well. In the case of bovine pancreatic phospholipase A2, this description markedly improves agreement with the observed x-ray diffraction data compared to the results of the classical one-model structure description. Time-averaged crystallographically restrained molecular dynamics reveals large mobilities in the loops involved in lipid bilayer association.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gros, P -- van Gunsteren, W F -- Hol, W G -- New York, N.Y. -- Science. 1990 Sep 7;249(4973):1149-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BIOSON Research Institute, University of Groningen, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2396108" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cattle ; Crystallography ; Hot Temperature ; Models, Molecular ; Motion ; *Phospholipases ; *Phospholipases A ; Phospholipases A2 ; Protein Conformation ; X-Ray Diffraction
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  • 51
    Publication Date: 1990-07-20
    Description: The 70-residue carboxyl-terminal domain of the muscle contractile protein troponin-C contains two helix-loop-helix calcium (Ca)-binding sites that are related to each other by approximate twofold rotational symmetry. Hydrophobic residues from the helices and a short three residue beta sheet at the interface of the two sites act to stabilize the protein domain in the presence of Ca. A synthetic 34-residue peptide representing one of these sites (site III) has been synthesized and studied by H-1 nuclear magnetic resonance (NMR) spectroscopy. In solution this peptide undergoes a Ca-induced conformational change to form the helix-loop-helix Ca-binding motif. Two-dimensional nuclear Overhauser effect spectra have provided evidence for the formation of a beta sheet and interactions between several hydrophobic residues from opposing helices as found in troponin-C. It is proposed that a symmetric two-site dimer similar in tertiary structure to the carboxyl-terminal domain of troponin-C forms from the assembly of two site III peptides in the Ca-bound form.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaw, G S -- Hodges, R S -- Sykes, B D -- New York, N.Y. -- Science. 1990 Jul 20;249(4966):280-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Alberta, Edmonton, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2374927" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Calcium/*metabolism/pharmacology ; Hydrogen ; Magnetic Resonance Spectroscopy/methods ; Models, Molecular ; Molecular Sequence Data ; Peptides/chemical synthesis/*metabolism ; Protein Conformation ; Troponin/chemical synthesis/*metabolism ; Troponin C ; Turkeys
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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-02-23
    Description: Reactive or unstable molecules are key intermediates in many important reactions, but can be difficult to prepare for experimental studies. Species with missing (:CH-OH) or extra (H3) substituents can often be formed conveniently in the gas phase by neutralizing a beam of a more stable ionic counterpart (CH = O+H, H3+). Reionization of the neutral after approximately 10(-6) seconds tests its stability, whereas its unimolecular chemistry can be probed by preparing it with different amounts of internal energy. The resulting neutral products are reionized and mass analyzed. Isomers are then characterized by ion dissociation and a third mass-analysis step. Many unusual molecules have been characterized with this technique, which can also be used to probe complex unimolecular chemistry, such as that of cyclobutadiene and ethylene oxide.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLafferty, F W -- GM-16609/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Feb 23;247(4945):925-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cornell University, Baker Laboratory, Ithaca, NY 14853-1301.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2305261" target="_blank"〉PubMed〈/a〉
    Keywords: Butadienes ; Chemical Phenomena ; Chemistry ; Ethylene Oxide ; Free Radicals ; Hydrocarbons ; *Ions ; *Mass Spectrometry ; Methane/analogs & derivatives ; Molecular Structure ; Thermodynamics
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-07-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pool, R -- New York, N.Y. -- Science. 1990 Jul 27;249(4967):364-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2377892" target="_blank"〉PubMed〈/a〉
    Keywords: *Magnetic Resonance Spectroscopy ; Molecular Structure ; National Institutes of Health (U.S.) ; Protein Conformation ; *Proteins ; United States
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  • 54
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-03-23
    Description: A strategy of iterative site-directed mutagenesis and binding analysis was used to incorporate the receptor-binding determinants from human growth hormone (hGH) into the nonbinding homolog, human prolactin (hPRL). The complementary DNA for hPRL was cloned, expressed in Escherichia coli, and mutated to introduce sequentially those substitutions from hGH that were predicted by alanine-scanning mutagenesis and other studies to be most critical for binding to the hGH receptor from human liver. After seven rounds of site-specific mutagenesis, a variant of hPRL was obtained containing eight mutations with an association constant for the hGH receptor that was increased more than 10,000-fold. This hPRL variant binds one-sixth as strongly as wild-type hGH, but shares only 26 percent overall sequence identity with hGH. These studies show the feasibility of recruiting receptor-binding properties from distantly related and functionally divergent hormones and show that a detailed functional database can be used to guide the design of a protein-protein interface in the absence of direct structural information.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cunningham, B C -- Henner, D J -- Wells, J A -- New York, N.Y. -- Science. 1990 Mar 23;247(4949 Pt 1):1461-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Engineering, Genentech, Inc. South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2321008" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cloning, Molecular ; Growth Hormone/genetics ; Humans ; Molecular Sequence Data ; Mutation ; Plasmids ; Prolactin/genetics/*metabolism ; Protein Conformation ; Receptors, Somatotropin/*metabolism ; Recombinant Proteins/metabolism
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  • 55
    Publication Date: 1990-09-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Y C -- Grable, J C -- Love, R -- Greene, P J -- Rosenberg, J M -- GM25671/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 14;249(4974):1307-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of Pittsburgh, PA 15260.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2399465" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Computer Graphics ; Crystallization ; DNA-Binding Proteins ; *Deoxyribonuclease EcoRI ; Methods ; Models, Molecular ; Molecular Sequence Data ; Oligonucleotides ; Protein Conformation ; X-Ray Diffraction
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  • 56
    Publication Date: 1990-05-11
    Description: It is a challenge to construct synthetic immunogens that elicit antibodies (Abs) both directed to conformational epitopes and specific for a complex protein like human choriogonadotropin (hCG). A monoclonal antibody specific for hCG bound to regions around Lys45 of the alpha subunit (hCG alpha) and Asp112 of the beta subunit (hCG beta). A peptide comprising residues 46 to 55 of hCG alpha and residues 106 to 116 of hCG beta elicited Abs in rabbits that were directed to a discontinuous epitope and were specific for hCG. These Abs inhibited the binding of hCG to its receptor. Thus, a synthetic immunogen can mimic a conformational-specific epitope and can be useful for vaccine development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bidart, J M -- Troalen, F -- Ghillani, P -- Rouas, N -- Razafindratsita, A -- Bohuon, C -- Bellet, D -- New York, N.Y. -- Science. 1990 May 11;248(4956):736-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departement de Biologie Clinique, Institut Gustave-Roussy, Villejuif, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1692160" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigen-Antibody Complex ; Chorionic Gonadotropin/genetics/*immunology ; Chorionic Gonadotropin, beta Subunit, Human ; Epitopes/*analysis/genetics ; Glycoprotein Hormones, alpha Subunit/immunology ; Humans ; Immune Sera ; Lysine ; Molecular Sequence Data ; Peptide Fragments/immunology ; Protein Conformation ; Rabbits/immunology ; Sequence Homology, Nucleic Acid
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  • 57
    Publication Date: 1990-02-23
    Description: Ras proteins participate as a molecular switch in the early steps of the signal transduction pathway that is associated with cell growth and differentiation. When the protein is in its GTP complexed form it is active in signal transduction, whereas it is inactive in its GDP complexed form. A comparison of eight three-dimensional structures of ras proteins in four different crystal lattices, five with a nonhydrolyzable GTP analog and three with GDP, reveals that the "on" and "off" states of the switch are distinguished by conformational differences that span a length of more than 40 A, and are induced by the gamma-phosphate. The most significant differences are localized in two regions: residues 30 to 38 (the switch I region) in the second loop and residues 60 to 76 (the switch II region) consisting of the fourth loop and the short alpha-helix that follows the loop. Both regions are highly exposed and form a continuous strip on the molecular surface most likely to be the recognition sites for the effector and receptor molecule(or molecules). The conformational differences also provide a structural basis for understanding the biological and biochemical changes of the proteins due to oncogenic mutations, autophosphorylation, and GTP hydrolysis, and for understanding the interactions with other proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Milburn, M V -- Tong, L -- deVos, A M -- Brunger, A -- Yamaizumi, Z -- Nishimura, S -- Kim, S H -- CA45593/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Feb 23;247(4945):939-45.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2406906" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallization ; Crystallography ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; Humans ; Models, Molecular ; Molecular Structure ; Protein Conformation ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins p21(ras) ; *Signal Transduction ; Structure-Activity Relationship
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  • 58
    Publication Date: 1990-09-21
    Description: Ribonuclease H digests the RNA strand of duplex RNA.DNA hybrids into oligonucleotides. This activity is indispensable for retroviral infection and is involved in bacterial replication. The ribonuclease H from Escherichia coli is homologous with the retroviral proteins. The crystal structure of the E. coli enzyme reveals a distinctive alpha-beta tertiary fold. Analysis of the molecular model implicates a carboxyl triad in the catalytic mechanism and suggests a likely mode for the binding of RNA.DNA substrates. The structure was determined by the method of multiwavelength anomalous diffraction (MAD) with the use of synchrotron data from a crystal of the recombinant selenomethionyl protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, W -- Hendrickson, W A -- Crouch, R J -- Satow, Y -- GM 34102/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Sep 21;249(4975):1398-405.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2169648" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Computer Graphics ; *Endoribonucleases/genetics ; Escherichia coli/enzymology ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Recombinant Proteins ; Ribonuclease H ; *Selenium ; *Selenomethionine ; Sequence Homology, Nucleic Acid ; X-Ray Diffraction/methods
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  • 59
    Publication Date: 1990-08-31
    Description: The isocitrate dehydrogenase of Escherichia coli is regulated by covalent modification at the active site rather than, as expected, at an allosteric site. As a means of evaluating the mechanism of regulation, the kinetics of the substrate, 2R,3S-isocitrate, and a substrate analog, 2R-malate, were compared for the native, phosphorylated, and mutant enzymes. Phosphorylation decreases activity by more than a factor of 10(6) for the true substrate, but causes minor changes in the activity of the substrate analog. The kinetic results indicate that electrostatic repulsion and steric hindrance between the phosphoryl moiety and the gamma carboxyl group of 2R,3S-isocitrate are the major causes of the inactivation, with a lesser contribution from the loss of a hydrogen bond.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dean, A M -- Koshland, D E Jr -- New York, N.Y. -- Science. 1990 Aug 31;249(4972):1044-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2204110" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Site ; Amino Acid Sequence ; Binding Sites ; Escherichia coli/*enzymology/genetics ; Isocitrate Dehydrogenase/genetics/*metabolism ; Models, Molecular ; Mutation ; Protein Conformation
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  • 60
    Publication Date: 1990-03-09
    Description: The gene encoding the yeast mitochondrial outer membrane channel VDAC was subjected to site-directed mutagenesis to change amino acids at 29 positions to residues differing in charge from the wild-type sequence. The mutant genes were then expressed in yeast, and the physiological consequences of single and multiple amino acid changes were assessed after isolation and insertion of mutant channels into phospholipid bilayers. Selectivity changes were observed at 14 sites distributed throughout the length of the molecule. These sites are likely to define the position of the protein walls lining the aqueous pore and hence, the transmembrane segments. These results have been used to develop a model of the open state of the channel in which each polypeptide contributes 12 beta strands and one alpha helix to form the aqueous transmembrane pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blachly-Dyson, E -- Peng, S -- Colombini, M -- Forte, M -- GM35759/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Mar 9;247(4947):1233-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1690454" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cloning, Molecular ; Intracellular Membranes/physiology ; *Ion Channels ; Lipid Bilayers/metabolism ; Membrane Potentials ; Membrane Proteins/*genetics/physiology ; Mitochondria/ultrastructure ; Molecular Sequence Data ; *Mutation ; *Porins ; Protein Conformation ; Saccharomyces cerevisiae/*genetics/ultrastructure ; Structure-Activity Relationship ; Voltage-Dependent Anion Channels
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 61
    Publication Date: 1990-11-23
    Description: While it has been known for some time that the c-Myc protein binds to random DNA sequences, no sequence-specific binding activity has been detected. At its carboxyl terminus, c-Myc contains a basic--helix-loop-helix (bHLH) motif, which is important for dimerization and specific DNA binding, as demonstrated for other bHLH protein family members. Of those studied, most bHLH proteins bind to sites that contain a CA- -TG consensus. In this study, the technique of selected and amplified binding-sequence (SAAB) imprinting was used to identify a DNA sequence that was recognized by c-Myc. A purified carboxyl-terminal fragment of human c-Myc that contained the bHLH domain bound in vitro in a sequence-specific manner to the sequence, CACGTG. These results suggest that some of the biological functions of Myc family proteins are accomplished by sequence-specific DNA binding that is mediated by the carboxyl-terminal region of the protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blackwell, T K -- Kretzner, L -- Blackwood, E M -- Eisenman, R N -- Weintraub, H -- R01 CA20525/CA/NCI NIH HHS/ -- T32 CA09437/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 23;250(4984):1149-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2251503" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; DNA/*metabolism ; Glutathione Transferase ; Leucine Zippers ; Macromolecular Substances ; Molecular Sequence Data ; Oligonucleotides/metabolism ; Polymerase Chain Reaction ; Protein Conformation ; Proto-Oncogene Proteins c-myc/*metabolism ; Recombinant Fusion Proteins/metabolism ; Templates, Genetic
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  • 62
    Publication Date: 1990-11-23
    Description: A technique was developed for studying protein-DNA recognition that can be applied to any purified protein, partially purified protein, or cloned gene. From oligonucleotides in which particular positions are of random sequence, that subset to which a given protein binds is amplified by the polymerase chain reaction and sequenced as a pool. These selected and amplified binding site (SAAB) "imprints" provide a characteristic set of preferred sequences for protein binding. With this technique, it was shown that homo- and heterooligomers of the helix-loop-helix proteins MyoD and E2A recognize a common consensus sequence, CA--TG, but otherwise bind to flanking and internal positions with different sequence preferences that suggest half-site recognition. These findings suggest that different combinations of dimeric proteins can have different binding sequence preferences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blackwell, T K -- Weintraub, H -- New York, N.Y. -- Science. 1990 Nov 23;250(4984):1104-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Fred Hutchinson Cancer Research Center, Seattle, WA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2174572" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; DNA/*metabolism ; DNA-Binding Proteins/*metabolism ; Glutathione Transferase ; Macromolecular Substances ; Molecular Sequence Data ; Muscle Proteins/*metabolism ; MyoD Protein ; Oligonucleotides/metabolism ; Polymerase Chain Reaction ; Protein Conformation ; Recombinant Fusion Proteins/metabolism ; Repetitive Sequences, Nucleic Acid ; TCF Transcription Factors ; Templates, Genetic ; Transcription Factor 7-Like 1 Protein ; *Transcription Factors
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 63
    Publication Date: 1990-08-03
    Description: A two-fold (C2) symmetric inhibitor of the protease of human immunodeficiency virus type-1 (HIV-1) has been designed on the basis of the three-dimensional symmetry of the enzyme active site. The symmetric molecule inhibited both protease activity and acute HIV-1 infection in vitro, was at least 10,000-fold more potent against HIV-1 protease than against related enzymes, and appeared to be stable to degradative enzymes. The 2.8 angstrom crystal structure of the inhibitor-enzyme complex demonstrated that the inhibitor binds to the enzyme in a highly symmetric fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Erickson, J -- Neidhart, D J -- VanDrie, J -- Kempf, D J -- Wang, X C -- Norbeck, D W -- Plattner, J J -- Rittenhouse, J W -- Turon, M -- Wideburg, N -- AI 27220/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 3;249(4968):527-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer-Assisted Molecular Design, Abbott Laboratories, Abbott Park, IL 60064.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2200122" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Drug Design ; Endopeptidases/*metabolism ; Gene Products, pol/*metabolism ; HIV Protease ; HIV-1/*enzymology ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Protease Inhibitors/*pharmacology ; Protein Conformation ; Sugar Alcohols/*pharmacology ; Valine/*analogs & derivatives/pharmacology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 64
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-02-23
    Description: According to the endosymbiont hypothesis, mitochondria have lost the autonomy of their prokaryotic ancestors. They have to import most of their proteins from the cytosol because the mitochondrial genome codes for only a small percentage of the polypeptides that reside in the organelle. Recent findings show that the sorting of proteins into the mitochondrial subcompartments and their folding and assembly follow principles already developed in prokaryotes. The components involved may have structural and functional equivalents in bacteria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hartl, F U -- Neupert, W -- New York, N.Y. -- Science. 1990 Feb 23;247(4945):930-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Physiological Chemistry, University of Munich, Federal Republic of Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2406905" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Biological Evolution ; Biological Transport, Active ; Cytosol/metabolism ; Heat-Shock Proteins/metabolism ; Intracellular Membranes/metabolism ; Mitochondria/*metabolism ; Models, Biological ; Molecular Sequence Data ; Peptide Hydrolases/metabolism ; Protein Conformation ; Protein Precursors/metabolism ; Proteins/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 65
    Publication Date: 1990-01-26
    Description: Activity of the immunoglobulin heavy and kappa light chain gene enhancers depends on a complex interplay of ubiquitous and developmentally regulated proteins. Two complementary DNAs were isolated that encode proteins, denoted ITF-1 and ITF-2, that are expressed in a variety of cell types and bind the microE5/kappa 2 motif found in both heavy and kappa light chain enhancers. The complementary DNAs are the products of distinct genes, yet both ITF-1 and ITF-2 are structurally and functionally similar. The two proteins interact with one another through their putative helix-loop-helix motifs and each possesses a distinct domain that dictates transcription activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Henthorn, P -- Kiledjian, M -- Kadesch, T -- New York, N.Y. -- Science. 1990 Jan 26;247(4941):467-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Philadelphia, PA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2105528" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism ; Base Sequence ; Binding Sites ; Cell Line ; Cloning, Molecular ; DNA/genetics/*metabolism ; *Enhancer Elements, Genetic ; *Genes, Immunoglobulin ; Humans ; Immunoglobulin kappa-Chains/genetics ; Immunoglobulin mu-Chains/genetics ; Macromolecular Substances ; Mice ; Molecular Sequence Data ; Plasmids ; Protein Conformation ; Saccharomyces cerevisiae/genetics ; Transcription Factors/*metabolism ; Transcription, Genetic ; Transfection ; Transformation, Genetic
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 66
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-06-15
    Description: The bacterial photosynthetic reaction center (RC) is a pigmented intrinsic membrane protein that performs the primary charge separation event of photosynthesis, thereby converting light to chemical energy. The RC pigments are bound primarily by two homologous peptides, the L and M subunits, each containing five transmembrane helices. These alpha helices and pigments are arranged in an approximate C2 symmetry and form two possible electron transfer pathways. Only one of these pathways is actually used. In an attempt to identify nonhomologous residues that are responsible for functional differences between the two branches, homologous helical regions that interact extensively with the pigments were genetically symmetrized (that is, exchanged). For example, replacement of the fourth transmembrane helix (D helix) in the M subunit with the homologous helix from the L subunit yields photosynthetically inactive RCs lacking a critical photoactive pigment. Photosynthetic revertants have been isolated in which single amino acid substitutions (intragenic suppressors) compensate for this partial symmetrization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robles, S J -- Breton, J -- Youvan, D C -- RIGM42645A/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Jun 15;248(4961):1402-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Program in Applied Biological Sciences, Massachusetts Institute of Technology, Cambridge 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2192455" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Bacterial Proteins/genetics ; Cloning, Molecular ; Electron Transport ; Macromolecular Substances ; Molecular Sequence Data ; Molecular Structure ; Mutation ; Photosynthesis ; Photosynthetic Reaction Center Complex Proteins ; Protein Conformation ; Rhodopseudomonas/analysis/genetics/growth & development ; Spectrophotometry
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  • 67
    Publication Date: 1990-08-24
    Description: The ligand-binding function of integrin adhesion receptors depends on divalent cations. A mutant alpha IIb beta 3 integrin (platelet gpIIb/IIIa) that lacks ligand recognition shows immunologic evidence of a perturbed interaction with divalent cations. This was found to be caused by a G----T mutation that resulted in an Asp119----Tyr119 substitution in the beta 3 subunit. This residue is proximal to bound ligand and is in a conserved region among integrins that are enriched in oxygenated residues. The spacing of these residues aligns with the calcium-binding residues in EF hand proteins, suggesting interaction with receptor-bound divalent cation as a mechanism of ligand binding common to all integrins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Loftus, J C -- O'Toole, T E -- Plow, E F -- Glass, A -- Frelinger, A L 3rd -- Ginsberg, M H -- AR 27214/AR/NIAMS NIH HHS/ -- HL 28235/HL/NHLBI NIH HHS/ -- HL 42977/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1990 Aug 24;249(4971):915-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Committee on Vascular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2392682" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Aspartic Acid ; Base Sequence ; Binding Sites ; Cell Line ; Integrins/*genetics/metabolism ; Ligands ; Macromolecular Substances ; Molecular Sequence Data ; *Mutation ; Oligonucleotide Probes ; Platelet Membrane Glycoproteins/*genetics/metabolism ; Polymerase Chain Reaction ; Protein Conformation ; Sequence Homology, Nucleic Acid ; Tyrosine
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  • 68
    Publication Date: 1990-05-18
    Description: The immunosuppressive agents cyclosporin A and FK506 inhibit the transcription of early T cell activation genes. The binding proteins for cyclosporin A and FK506, cyclophilin and FKBP, respectively, are peptidyl-prolyl-cis-trans isomerases, or rotamases. One proposed mechanism for rotamase catalysis by cyclophilin involves a tetrahedral adduct of an amide carbonyl and an enzyme-bound nucleophile. The potent FKBP rotamase inhibitor FK506 has a highly electrophilic carbonyl that is adjacent to an acyl-pipicolinyl (homoprolyl) amide bond. Such a functional group would be expected to form a stabilized, enzyme-bound tetrahedral adduct. Spectroscopic and chemical evidence reveals that the drug interacts noncovalently with its receptor, suggesting that the alpha-keto amid of FK506 serves as a surrogate for the twisted amide of a bound peptide substrate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosen, M K -- Standaert, R F -- Galat, A -- Nakatsuka, M -- Schreiber, S L -- GM-38627/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 May 18;248(4957):863-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1693013" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Isomerases/*antagonists & inhibitors ; Anti-Bacterial Agents/metabolism/*pharmacology ; Binding Sites ; Carrier Proteins/antagonists & inhibitors/metabolism ; Chemical Phenomena ; Chemistry ; Cloning, Molecular ; Cyclosporins/metabolism/pharmacology ; Escherichia coli/genetics ; Gene Expression ; *Immunosuppressive Agents ; Lymphocyte Activation ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Peptidylprolyl Isomerase ; Recombinant Proteins ; T-Lymphocytes/immunology ; Tacrolimus
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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