2y6e: Difference between revisions
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== | ==Structure of the D1D2 domain of USP4, the conserved catalytic domain== | ||
<StructureSection load='2y6e' size='340' side='right' caption='[[2y6e]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='2y6e' size='340' side='right' caption='[[2y6e]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
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<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
USP4 is | 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<ref>PMID:25404403</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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[[Category: Human]] | [[Category: Human]] | ||
[[Category: Ubiquitin thiolesterase]] | [[Category: Ubiquitin thiolesterase]] | ||
[[Category: Dijk, W J.van | [[Category: Dijk, W J.van]] | ||
[[Category: Faesen, A C | [[Category: Faesen, A C]] | ||
[[Category: Fish, A | [[Category: Fish, A]] | ||
[[Category: Luna-Vargas, M P.A | [[Category: Luna-Vargas, M P.A]] | ||
[[Category: Rape, M | [[Category: Rape, M]] | ||
[[Category: Sixma, T K | [[Category: Sixma, T K]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
Revision as of 10:48, 3 December 2014
Structure of the D1D2 domain of USP4, the conserved catalytic domainStructure of the D1D2 domain of USP4, the conserved catalytic domain
Structural highlights
Publication Abstract from PubMedUbiquitin-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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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