Document Type

Article

Publication Title

Journal of Biological Chemistry

Publication Date

6-11-1999

Volume

274

Issue

24

Disciplines

Biology | Life Sciences

Abstract

The structure of the G protein G(i 1/4 ) complexed with the nonhydrolyzable GTP analog guanosine-5'-(βγ-imino)triphosphate (GppNHp) has been determined at a resolution of 1.5 Å. In the active site of G(i 1/4 )·GppNHp, a water molecule is hydrogen bonded to the side chain of Glu43 and to an oxygen atom of the γ-phosphate group. The side chain of the essential catalytic residue Gln204 assumes a conformation which is distinctly different from that observed in complexes with either guanosine 5'-O-3-thiotriphosphate or the transition state analog GDP·A1F4-. Hydrogen bonding and steric interactions position Gln204 such that it interacts with a presumptive nucleophilic water molecule, but cannot interact with the pentacoordinate transition state. Gln204 must be released from this auto-inhibited state to participate in catalysis. RGS proteins may accelerate the rate of GTP hydrolysis by G protein α subunits, in part, by inserting an amino acid side chain into the site occupied by Gln204, thereby destabilizing the auto- inhibited state of Gα.

DOI

https://doi.org/10.1074/jbc.274.24.16669

Rights

© 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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