1wer
From Proteopedia
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RAS-GTPASE-ACTIVATING DOMAIN OF HUMAN P120GAP
Contents |
Overview
Ras-related GTP-binding proteins function as molecular switches which, cycle between GTP-bound 'on'- and GDP-bound 'off'-states. GTP hydrolysis, is the common timing mechanism that mediates the return from the 'on' to, the 'off'-state. It is usually slow but can be accelerated by orders of, magnitude upon interaction with GTPase-activating proteins (GAPs). In the, case of Ras, a major regulator of cellular growth, point mutations are, found in approximately 30% of human tumours which render the protein, unable to hydrolyse GTP, even in the presence of Ras-GAPs. The first, structure determination of a GTPase-activating protein reveals the, catalytically active fragment of the Ras-specific p120GAP (ref. 2), GAP-334, as an elongated, exclusively helical protein which appears to, represent a novel protein fold. The molecule consists of two domains, one, of which contains all the residues conserved among different GAPs for Ras., From the location of conserved residues around a shallow groove in the, central domain we can identify the site of interaction with Ras x GTP., This leads to a model for the interaction between Ras and GAP that, satisfies numerous biochemical and genetic data on this important, regulatory process.
Disease
Known diseases associated with this structure: Basal cell carcinoma, somatic OMIM:[139150], Capillary malformation-arteriovenous malformation OMIM:[139150], Parkes Weber syndrome OMIM:[139150]
About this Structure
1WER is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras., Scheffzek K, Lautwein A, Kabsch W, Ahmadian MR, Wittinghofer A, Nature. 1996 Dec 12;384(6609):591-6. PMID:8955277
Page seeded by OCA on Fri Feb 15 17:05:50 2008
