1CIP

GI-ALPHA-1 SUBUNIT OF GUANINE NUCLEOTIDE-BINDING PROTEIN COMPLEXED WITH A GTP ANALOGUE

Summary for 1CIP

• Entry DOI: 10.2210/pdb1cip/pdb
• Descriptor: PROTEIN (GUANINE NUCLEOTIDE-BINDING PROTEIN ALPHA-1 SUBUNIT), MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (4 entities in total)
• Functional Keywords: gtpase, g protein, hydrolase
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Nucleus: P10824
• Total number of polymer chains: 1
• Total formula weight: 40814.34

Authors

Coleman, D.,Sprang, S. (deposition date: 1999-04-05, release date: 1999-04-09, Last modification date: 2023-08-09)

Primary citation

Coleman, D.E.,Sprang, S.R.
Structure of Gialpha1.GppNHp, autoinhibition in a galpha protein-substrate complex.
J.Biol.Chem., 274:16669-16672, 1999

PubMed Abstract: The structure of the G protein Gialpha1 complexed with the nonhydrolyzable GTP analog guanosine-5'-(betagamma-imino)triphosphate (GppNHp) has been determined at a resolution of 1.5 A. In the active site of Gialpha1. GppNHp, a water molecule is hydrogen bonded to the side chain of Glu43 and to an oxygen atom of the gamma-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.AlF4-. 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 alpha subunits, in part, by inserting an amino acid side chain into the site occupied by Gln204, thereby destabilizing the auto-inhibited state of Galpha.

PubMed: 10358003
DOI: 10.1074/jbc.274.24.16669

Experimental method

X-RAY DIFFRACTION (1.5 Å)