Mechanism of GTP hydrolysis by G-protein alpha subunits.

Kleuss C, Raw AS, Lee E, Sprang SR, Gilman AG
Proc Natl Acad Sci U S A. 1994 91 (21): 9828-31

PMID: 7937899 · PMCID: PMC44910 · DOI:10.1073/pnas.91.21.9828

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.

MeSH Terms (24)

Aluminum Compounds Amino Acid Sequence Base Sequence Conserved Sequence DNA Escherichia coli Fluorides GTP-Binding Proteins GTP Phosphohydrolases Guanosine 5'-O-(3-Thiotriphosphate) Guanosine Triphosphate Humans Hydrolysis Kinetics Macromolecular Substances Magnesium Molecular Sequence Data Mutagenesis, Site-Directed Oligodeoxyribonucleotides Phosphorus Radioisotopes Proto-Oncogene Proteins p21(ras) Recombinant Proteins Signal Transduction Time Factors

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