2y6e

Structure of the D1D2 domain of USP4, the conserved catalytic domainStructure of the D1D2 domain of USP4, the conserved catalytic domain

Structural highlights 2y6e is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , NonStd Res: Activity: Ubiquitin thiolesterase, with EC number 3.1.2.15 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Ubiquitin-specific protease USP4 is emerging as an important regulator of cellular pathways, including the TGF-beta response, NF-kappaB signalling and splicing, with possible roles in cancer. Here we show that USP4 has its catalytic triad arranged in a productive conformation. Nevertheless, it requires its N-terminal DUSP-Ubl domain to achieve full catalytic turnover. Pre-steady-state kinetics measurements reveal that USP4 catalytic domain activity is strongly inhibited by slow dissociation of ubiquitin after substrate hydrolysis. The DUSP-Ubl domain is able to enhance ubiquitin dissociation, hence promoting efficient turnover. In a mechanism that requires all USP4 domains, binding of the DUSP-Ubl domain promotes a change of a switching loop near the active site. This 'allosteric regulation of product discharge' provides a novel way of regulating deubiquitinating enzymes that may have relevance for other enzyme classes. The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange.,Clerici M, Luna-Vargas MP, Faesen AC, Sixma TK Nat Commun. 2014 Nov 18;5:5399. doi: 10.1038/ncomms6399. PMID:25404403 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thioesterase

spinqualitylabelsall models 2y6e, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image