@article{183c6af362d44bb0baa4ff8c0926ae3a,
title = "Structure of RGS4 bound to AlF4--activated G(iα1): Stabilization of the transition state for GTP hydrolysis",
abstract = "RGS proteins are GTPase activators for heterotrimeric G proteins. We report here the 2.8 {\AA} resolution crystal structure of the RGS protein RGS4 complexed with G(iα1)-Mg2+-GDP-AlF4. Only the core domain of RGS4 is visible in the crystal. The core domain binds to the three switch regions of G(iα1), but does not contribute catalytic residues that directly interact with either GDP or AlF4. Therefore, RGS4 appears to catalyze rapid hydrolysis of GTP primarily by stabilizing the switch regions of G(iα1), although the conserved Asn-128 from RGS4 could also play a catalytic role by interacting with the hydrolytic water molecule or the side chain of Gln-204. The binding site for RGS4 on G(iα1) is also consistent with the activity of RGS proteins as antagonists of G(α) effectors.",
author = "Tesmer, {John J G} and Berman, {David M.} and Gilman, {Alfred G.} and Sprang, {Stephen R.}",
note = "Funding Information: Correspondence regarding this paper should be addressed to S. R. S. We would like to thank Bryan Sutton, Tsan Xiao, Bertram Canagarajah, Ward Coats, and the MacCHESS staff for their assistance with data collection at CHESS; Bryan Sutton and Lothar Esser for their assistance in preparing the figures; and Clive Slaughter for mass spectrometry of RGS4. D. M. B. is a member of the University of Texas Southwestern Graduate School Cell Regulation Program and was supported by the Medical Scientist Training Program and Pharmacological Sciences Training Grant GM07062. This work was supported by NIH grant DK46371 and Welch Foundation grant I-1229 to S. R. S, and by NIH grant GM34497, American Cancer Society grant RPG-77–001–21-BE, Welch Foundation grant I-1271, and the Raymond and Ellen Willie Distinguished Chair of Molecular Neuropharmacology to A. G. G. ",
year = "1997",
month = apr,
day = "18",
doi = "10.1016/S0092-8674(00)80204-4",
language = "English (US)",
volume = "89",
pages = "251--261",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}