RGD Reference Report - Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis. - Rat Genome Database

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Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis.

Authors: Coleman, D E  Berghuis, A M  Lee, E  Linder, M E  Gilman, A G  Sprang, S R 
Citation: Coleman DE, etal., Science. 1994 Sep 2;265(5177):1405-12.
RGD ID: 12792992
Pubmed: PMID:8073283   (View Abstract at PubMed)

Mechanisms of guanosine triphosphate (GTP) hydrolysis by members of the G protein alpha subunit-p21ras superfamily of guanosine triphosphatases have been studied extensively but have not been well understood. High-resolution x-ray structures of the GTP gamma S and GDP.AlF4- complexes formed by the G protein Gi alpha 1 demonstrate specific roles in transition-state stabilization for two highly conserved residues. Glutamine204 (Gln61 in p21ras) stabilizes and orients the hydrolytic water in the trigonal-bipyramidal transition state. Arginine 178 stabilizes the negative charge at the equatorial oxygen atoms of the pentacoordinate phosphate intermediate. Conserved only in the G alpha family, this residue may account for the higher hydrolytic rate of G alpha proteins relative to those of the p21ras family members. The fold of Gi alpha 1 differs from that of the homologous Gt alpha subunit in the conformation of a helix-loop sequence located in the alpha-helical domain that is characteristic of these proteins; this site may participate in effector binding. The amino-terminal 33 residues are disordered in GTP gamma S-Gi alpha 1, suggesting a mechanism that may promote release of the beta gamma subunit complex when the alpha subunit is activated by GTP.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
GDP binding enablesIDA 12792992PMID:8073283CAFA 
GTP binding enablesIMP 12792992PMID:8073283CAFA 
magnesium ion binding enablesIMP 12792992PMID:8073283CAFA 

Objects Annotated

Genes (Rattus norvegicus)
Gnai1  (G protein subunit alpha i1)


Additional Information