Abstract
Hydrolysis of GTP by a variety of guanine nucleotide-binding proteins is a crucial step for regulation of these biological switches. Mutations that impair the GTPase activity of certain heterotrimeric signal-transducing G proteins or of p21ras cause tumors in man. A conserved glutamic residue in the alpha subunit of G proteins has been hypothesized to serve as a general base, thereby activating a water molecule for nucleophilic attack on GTP. The results of mutagenesis of this residue (Glu-207) in Gi alpha 1 refute this hypothesis. Based on the structure of the complex of Gi alpha 1 with GDP, Mg2+, and AlF-4, which appears to resemble the transition state for GTP hydrolysis, we believe that Gln-204 of Gi alpha 1, rather than Glu-207, supports catalysis of GTP hydrolysis by stabilization of the transition state.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aluminum Compounds / metabolism
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Amino Acid Sequence
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Base Sequence
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Conserved Sequence
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DNA / chemistry
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Escherichia coli
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Fluorides / metabolism
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GTP Phosphohydrolases / metabolism*
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GTP-Binding Proteins / isolation & purification
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GTP-Binding Proteins / metabolism*
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism*
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Guanosine Triphosphate / metabolism*
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Humans
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Hydrolysis
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Kinetics
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Macromolecular Substances
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Magnesium / metabolism
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Oligodeoxyribonucleotides
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Phosphorus Radioisotopes
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Proto-Oncogene Proteins p21(ras) / metabolism
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Signal Transduction
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Time Factors
Substances
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Aluminum Compounds
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Macromolecular Substances
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Oligodeoxyribonucleotides
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Phosphorus Radioisotopes
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Recombinant Proteins
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tetrafluoroaluminate
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Guanosine 5'-O-(3-Thiotriphosphate)
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Guanosine Triphosphate
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DNA
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GTP Phosphohydrolases
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GTP-Binding Proteins
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)
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Magnesium
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Fluorides