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  • Base Sequence  (2)
  • Binding Sites  (1)
  • ELECTRONIC COMPONENTS AND CIRCUITS
  • LUNAR AND PLANETARY EXPLORATION
  • 1990-1994  (3)
  • 1965-1969
  • 1990  (3)
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  • 1990-1994  (3)
  • 1965-1969
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  • 1
    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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2011-08-19
    Description: The discovery of 154 meteorite fragments within an 11-sq km area of wind-excavated basins in Roosevelt County, New Mexico, permits a new calculation of the accumulation rate of meteorite falls at the earth's surface. Thermoluminescence dating of the coversand unit comprising the prime recovery surface suggests the maximum terrestrial age of the meteorites to be about 16.0 ka. The 68 meteorite fragments subjected to petrological analyses represent a minimum of 49 individual falls. Collection bias has largely excluded carbonaceous chondrites and achondrites, requiring the accumulation rate derived from the recovered samples to be increased by a factor of 1.25. Terrestrial weathering destroying ordinary chondrites can be modeled as a first-order decay process with an estimated half-life of 3.5 + or - 1.9 ka on the semiarid American High Plains. Having accounted for the age of the recovery surface, area of field searches, pairing of finds, collection bias and weathering half-life, an accumulation rate of 940 falls/a per 10 to the 6th sq km is calculated for falls greater than 10 g total mass. This figure exceeds the best-constrained previous estimate by more than an order of magnitude. One possible reason for this disparity may be the extraordinary length of the fall record preserved in the surficial geology of Roosevelt County. The high accumulation rate determined for the past 16 ka may point to the existence of periods when the meteorite fall rate was significantly greater than at present.
    Keywords: LUNAR AND PLANETARY EXPLORATION
    Type: Meteoritics (ISSN 0026-1114); 25; 11-17
    Format: text
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