Mechanism of GTP hydrolysis by G-protein α subunits

Christiane Kleuss, André S. Raw, Ethan Lee, Stephen R. Sprang, Alfred G. Gilman

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


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 p21(ras) cause tumors in man. A conserved glutamic residue in the α 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 G(iα1) refute this hypothesis. Based on the structure of the complex of G(iα1) with GDP, Mg2+, and AlF4/-, which appears to resemble the transition state for GTP hydrolysis, we believe that Glu-204 of G(iα1), rather than Glu-207, supports catalysis of GTP hydrolysis by stabilization of the transition state.

Original languageEnglish
Pages (from-to)9828-9831
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
StatePublished - Oct 11 1994


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