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 journalArticle

85 Citations (Scopus)

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 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 (US)
Pages (from-to)9828-9831
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number21
DOIs
StatePublished - Oct 11 1994

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Protein Subunits
Guanosine Triphosphate
GTP-Binding Proteins
Hydrolysis
Proto-Oncogene Proteins p21(ras)
Guanine Nucleotides
GTP Phosphohydrolases
Catalysis
Mutagenesis
Carrier Proteins
Mutation
Water
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Mechanism of GTP hydrolysis by G-protein α subunits. / Kleuss, Christiane; Raw, André S.; Lee, Ethan; Sprang, Stephen R.; Gilman, Alfred G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 21, 11.10.1994, p. 9828-9831.

Research output: Contribution to journalArticle

Kleuss, Christiane ; Raw, André S. ; Lee, Ethan ; Sprang, Stephen R. ; Gilman, Alfred G. / Mechanism of GTP hydrolysis by G-protein α subunits. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 21. pp. 9828-9831.
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