5f6y
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Ubc9 (K48/K49A/E54A) complexed with Fragment 2 (mercaptobenzoxazole)== | |
| + | <StructureSection load='5f6y' size='340' side='right' caption='[[5f6y]], [[Resolution|resolution]] 1.14Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5f6y]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F6Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F6Y FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5VM:5-CHLORANYL-3~{H}-1,3-BENZOXAZOLE-2-THIONE'>5VM</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f6d|5f6d]], [[5f6e|5f6e]], [[5f6u|5f6u]], [[5f6v|5f6v]], [[5f6w|5f6w]], [[5f6x|5f6x]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5f6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f6y OCA], [http://pdbe.org/5f6y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f6y RCSB], [http://www.ebi.ac.uk/pdbsum/5f6y PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/UBC9_HUMAN UBC9_HUMAN]] Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3 and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation.<ref>PMID:8668529</ref> <ref>PMID:11451954</ref> <ref>PMID:15809060</ref> <ref>PMID:19744555</ref> <ref>PMID:19638400</ref> <ref>PMID:17466333</ref> <ref>PMID:20077568</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Conjugation of the small ubiquitin-like modifier (SUMO) to protein substrates is an important disease-associated posttranslational modification, although few inhibitors of this process are known. Herein, we report the discovery of an allosteric small-molecule binding site on Ubc9, the sole SUMO E2 enzyme. An X-ray crystallographic screen was used to identify two distinct small-molecule fragments that bind to Ubc9 at a site distal to its catalytic cysteine. These fragments and related compounds inhibit SUMO conjugation in biochemical assays with potencies of 1.9-5.8 mm. Mechanistic and biophysical analyses, coupled with molecular dynamics simulations, point toward ligand-induced rigidification of Ubc9 as a mechanism of inhibition. | ||
| - | + | Insights Into the Allosteric Inhibition of the SUMO E2 Enzyme Ubc9.,Hewitt WM, Lountos GT, Zlotkowski K, Dahlhauser SD, Saunders LB, Needle D, Tropea JE, Zhan C, Wei G, Ma B, Nussinov R, Waugh DS, Schneekloth JS Jr Angew Chem Int Ed Engl. 2016 May 4;55(19):5703-7. doi: 10.1002/anie.201511351., Epub 2016 Apr 1. PMID:27038327<ref>PMID:27038327</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5f6y" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| - | + | <references/> | |
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Dahlhauser, S]] | [[Category: Dahlhauser, S]] | ||
| - | [[Category: | + | [[Category: Hewitt, W M]] |
| + | [[Category: Lountos, G T]] | ||
| + | [[Category: Ma, B]] | ||
| + | [[Category: Needle, D]] | ||
[[Category: Nussinov, R]] | [[Category: Nussinov, R]] | ||
| - | [[Category: | + | [[Category: Saunders, L B]] |
| - | [[Category: | + | [[Category: Schneekloth, J S.Jr]] |
| - | [[Category: | + | [[Category: Tropea, J E]] |
| - | [[Category: Waugh, D | + | [[Category: Waugh, D S]] |
| - | [[Category: | + | [[Category: Wei, G]] |
[[Category: Zhan, C]] | [[Category: Zhan, C]] | ||
| - | [[Category: | + | [[Category: Zlotkowski, K]] |
| + | [[Category: Fragment drug design]] | ||
| + | [[Category: Ligase-ligase inhibitor complex]] | ||
| + | [[Category: Sumoylation]] | ||
| + | [[Category: Ubc9]] | ||
Revision as of 19:27, 10 May 2016
Crystal structure of Ubc9 (K48/K49A/E54A) complexed with Fragment 2 (mercaptobenzoxazole)
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