1srq
From Proteopedia
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Crystal Structure of the Rap1GAP catalytic domain
Overview
Rap1 is a Ras-like guanine-nucleotide-binding protein (GNBP) that is, involved in a variety of signal-transduction processes. It regulates, integrin-mediated cell adhesion and might activate extracellular, signal-regulated kinase. Like other Ras-like GNBPs, Rap1 is regulated by, guanine-nucleotide-exchange factors (GEFs) and GTPase-activating proteins, (GAPs). These GAPs increase the slow intrinsic GTPase reaction of Ras-like, GNBPs by many orders of magnitude and allow tight regulation of, signalling. The activation mechanism involves stabilization of the, catalytic glutamine of the GNBP and, in most cases, the insertion of a, catalytic arginine of GAP into the active site. Rap1 is a close homologue, of Ras but does not possess the catalytic glutamine essential for GTP, hydrolysis in all other Ras-like and Galpha proteins. Furthermore, RapGAPs, are not related to other GAPs and apparently do not use a catalytic, arginine residue. Here we present the crystal structure of the catalytic, domain of the Rap1-specific Rap1GAP at 2.9 A. By mutational analysis, fluorescence titration and stopped-flow kinetic assay, we demonstrate that, Rap1GAP provides a catalytic asparagine to stimulate GTP hydrolysis., Implications for the disease tuberous sclerosis are discussed.
About this Structure
1SRQ is a Single protein structure of sequence from Homo sapiens with SO4 and MPD as ligands. Full crystallographic information is available from OCA.
Reference
The GTPase-activating protein Rap1GAP uses a catalytic asparagine., Daumke O, Weyand M, Chakrabarti PP, Vetter IR, Wittinghofer A, Nature. 2004 May 13;429(6988):197-201. PMID:15141215
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