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. 1994 Oct 11;91(21):9828–9831. doi: 10.1073/pnas.91.21.9828

Mechanism of GTP hydrolysis by G-protein alpha subunits.

C Kleuss 1, A S Raw 1, E Lee 1, S R Sprang 1, A G Gilman 1
PMCID: PMC44910  PMID: 7937899

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.

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Selected References

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