PDBsum entry: 1cip

Hydrolase

PDB id: 1cip

Contents

Protein chain

316 a.a. *

Ligands

GNP

Metals

_MG

Waters ×157

* Residue conservation analysis

PDB id:

1cip

Name:

Hydrolase

Title:

Gi-alpha-1 subunit of guanine nucleotide-binding protein complexed with a gtp analogue

Structure:

Protein (guanine nucleotide-binding protein alpha-1 subunit). Chain: a. Synonym: gia1, guanine nucleotide-binding protein g(i), alpha-1 subunit. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.50Å R-factor: 0.213 R-free: 0.235

Authors:

D.Coleman,S.Sprang

Key ref:

D.E.Coleman and S.R.Sprang (1999). Structure of Gialpha1.GppNHp, autoinhibition in a galpha protein-substrate complex. J Biol Chem, 274, 16669-16672. PubMed id: 10358003 DOI: 10.1074/jbc.274.24.16669

Date:

05-Apr-99 Release date: 09-Apr-99

Protein chain

P10824  (GNAI1_RAT) -  Guanine nucleotide-binding protein G(i) subunit alpha-1

Seq: 354 a.a.

Struc: 316 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (13 terms)
• Biological process: cell cycle (6 terms)
• Biochemical function: nucleotide binding (8 terms)

DOI no: 10.1074/jbc.274.24.16669

J Biol Chem 274:16669-16672 (1999)

PubMed id: 10358003

Structure of Gialpha1.GppNHp, autoinhibition in a galpha protein-substrate complex.

D.E.Coleman, S.R.Sprang.

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.

Selected figure(s)

Figure 1.
Fig. 1. Electron density about the active site of the G[i 1]·GppNHp complex. The 1.5-Å 2 F[o] F[c] electron density map (blue) was calculated using SigmaA-weighted phases derived from the model, contoured at 1.5 . The model is shown as a ball-and-stick representation. Red, oxygen; yellow, carbon; blue, nitrogen; green, phosphorous; silver, magnesium. The figure was generated using the program BOBSCRIPT (51) and rendered with RASTER3D (52), and POVRAY.

Figure 2.
Fig. 2. The active site of G[i 1] in the (GTP analog) and (transition state analog·RGS4) bound complexes. Key features are labeled. A, G[i 1]·GppNHp; B, G[i 1]·GTP S; C, RGS4·G[i 1]·GDP·AlF[4]^ ·H[2]O; and D, hypothetical RGS4·G[i 1]·GppNHp complex. The main chain segments of G[i 1] are colored green (P-loop residues 38-48), blue (Switch I residues 178-184), and yellow (Switch II residues 200-208). The main chain segment of RGS4 in panels C and D is shown in red (residues 126-131). The atoms and water molecules are colored as described in Fig. 1, except that the phosphorous atoms are in yellow, magnesium is blue, and the sulfur atom of GTP S is green. In panel D, the region of the hypothetical model where Asn^128 of RGS4 and Gln^204 of G[i 1] collide is highlighted in cyan.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1999, 274, 16669-16672) copyright 1999.