5l8h: Difference between revisions
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==Structure of USP46-UbVME== | |||
<StructureSection load='5l8h' size='340' side='right'caption='[[5l8h]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5l8h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L8H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L8H FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GVE:METHYL+4-AMINOBUTANOATE'>GVE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5l8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l8h OCA], [https://pdbe.org/5l8h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l8h RCSB], [https://www.ebi.ac.uk/pdbsum/5l8h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l8h ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/UBP46_HUMAN UBP46_HUMAN] Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action. May act by mediating the deubiquitination of GAD1/GAD67. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Not involved in deubiquitination of monoubiquitinated FANCD2.<ref>PMID:19075014</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Regulation of deubiquitinating enzyme (DUB) activity is an essential step for proper function of cellular ubiquitin signals. UAF1 is a WD40 repeat protein, which binds and activates three important DUBs, USP1, USP12 and USP46. Here, we report the crystal structure of the USP12-Ub/UAF1 complex at a resolution of 2.8A and of UAF1 at 2.3A. In the complex we find two potential sites for UAF1 binding, analogous to what was seen in a USP46/UAF1 complex. In line with these observed dual binding states, we show here that USP12/UAF1 complex has 1:2 stoichiometry in solution, with a two-step binding at 4nM and 325nM respectively. Mutagenesis studies show that the fingers sub-domain of USP12 interacts with UAF1 to form the high affinity interface. Our activation studies confirm that the high affinity binding is important for activation while the second UAF1 binding does not affect activation. Nevertheless, we show that this two step binding is conserved in the well-studied USP12 paralog, USP1. Our results highlight the interfaces essential for regulation of USP12 activity and show a conserved second binding of UAF1 which could be important for regulatory functions independent of USP12 activity. | |||
A conserved two-step binding for the UAF1 regulator to the USP12 deubiquitinating enzyme.,Dharadhar S, Clerici M, van Dijk WJ, Fish A, Sixma TK J Struct Biol. 2016 Sep 17. pii: S1047-8477(16)30200-3. doi:, 10.1016/j.jsb.2016.09.011. PMID:27650958<ref>PMID:27650958</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5l8h" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Thioesterase 3D structures|Thioesterase 3D structures]] | |||
*[[3D structures of ubiquitin|3D structures of ubiquitin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Clerici M]] | |||
[[Category: Dharadhar S]] | |||
[[Category: Sixma T]] |