4hlq

Crystal structure of human rab1b bound to GDP and BEF3 in complex with the GAP domain of TBC1D20 from homo sapiens

spinqualitylabelsall models 4hlq, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hlq is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.3Å Ligands: BEF, GDP, MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TBC20_HUMAN Micro syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function TBC20_HUMAN GTPase-activating protein specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude. Publication Abstract from PubMed Rab GTPases, key regulators of vesicular transport, hydrolyze GTP very slowly unless assisted by Rab GTPase-activating proteins (RabGAPs). Dysfunction of RabGAPs is involved in many diseases. By combining X-ray structure analysis and time-resolved FTIR spectroscopy we reveal here the detailed molecular reaction mechanism of a complex between human Rab and RabGAP at the highest possible spatiotemporal resolution and in atomic detail. A glutamine residue of Rab proteins (cis-glutamine) that is essential for intrinsic activity is less important in the GAP-activated reaction. During generation of the RabGAP.Rab:GTP complex, there is a rapid conformational change in which the cis-glutamine is replaced by a glutamine from RabGAP (trans-glutamine); this differs from the RasGAP mechanism, where the cis-glutamine is also important for GAP catalysis. However, as in the case of Ras, a trans-arginine is also recruited to complete the active center during this conformational change. In contrast to the RasGAP mechanism, an accumulation of a state in which phosphate is bound is not observed, and bond breakage is the rate-limiting step. The movement of trans-glutamine and trans-arginine into the catalytic site and bond breakage during hydrolysis are monitored in real time. The combination of X-ray structure analysis and time-resolved FTIR spectroscopy provides detailed insight in the catalysis of human Rab GTPases. Catalytic mechanism of a mammalian Rab{middle dot}RabGAP complex in atomic detail.,Gavriljuk K, Gazdag EM, Itzen A, Kotting C, Goody RS, Gerwert K Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21348-53. doi:, 10.1073/pnas.1214431110. Epub 2012 Dec 12. PMID:23236136 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ras-related protein Rab 3D structures

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