Mechanism of GTP hydrolysis by G-protein α subunits

Authors

Christiane Kleuss, University of Texas Southwestern Medical Center
André S. Raw, University of Texas Southwestern Medical Center
Ethan Lee, University of Texas Southwestern Medical Center
Stephen R. Sprang, University of Montana
Alfred G. Gilman, University of Texas Southwestern Medical Center

Document Type

Article

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

10-1994

Volume

91

Issue

21

Disciplines

Biology | Life Sciences

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.

DOI

https://doi.org/10.1073/pnas.91.21.9828

Recommended Citation

Kleuss, Christiane; Raw, André S.; Lee, Ethan; Sprang, Stephen R.; and Gilman, Alfred G., "Mechanism of GTP hydrolysis by G-protein α subunits" (1994). Biological Sciences Faculty Publications. 547.
https://scholarworks.umt.edu/biosci_pubs/547