6xoi: Difference between revisions

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-'''Unreleased structure'''
-The entry 6xoi is ON HOLD
+==Structure of SUMO1-ML00752641 adduct bound to SAE==
+<StructureSection load='6xoi' size='340' side='right'caption='[[6xoi]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6xoi]] is a 3 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=6XOI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XOI 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]] 2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VBA:[(1~{R},2~{R},3~{S},4~{R})-2,3-bis(oxidanyl)-4-[[5-[1-(phenylmethyl)pyrazol-3-yl]carbonylpyrimidin-4-yl]amino]cyclopentyl]methyl+sulfamate'>VBA</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=6xoi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xoi OCA], [https://pdbe.org/6xoi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xoi RCSB], [https://www.ebi.ac.uk/pdbsum/6xoi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xoi ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SAE1_HUMAN SAE1_HUMAN] The heterodimer acts as a E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.<ref>PMID:9920803</ref> <ref>PMID:10217437</ref> <ref>PMID:10187858</ref> <ref>PMID:11481243</ref> <ref>PMID:11451954</ref> <ref>PMID:15660128</ref> <ref>PMID:20164921</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+SUMOylation is a reversible post-translational modification that regulates protein function through covalent attachment of small ubiquitin-like modifier (SUMO) proteins. The process of SUMOylating proteins involves an enzymatic cascade, the first step of which entails the activation of a SUMO protein through an ATP-dependent process catalyzed by SUMO-activating enzyme (SAE). Here, we describe the identification of TAK-981, a mechanism-based inhibitor of SAE which forms a SUMO-TAK-981 adduct as the inhibitory species within the enzyme catalytic site. Optimization of selectivity against related enzymes as well as enhancement of mean residence time of the adduct were critical to the identification of compounds with potent cellular pathway inhibition and ultimately a prolonged pharmacodynamic effect and efficacy in preclinical tumor models, culminating in the identification of the clinical molecule TAK-981.
-Authors: Sintchak, M., Lane, W., Bump, N.
+Discovery of TAK-981, a First-in-Class Inhibitor of SUMO-Activating Enzyme for the Treatment of Cancer.,Langston SP, Grossman S, England D, Afroze R, Bence N, Bowman D, Bump N, Chau R, Chuang BC, Claiborne C, Cohen L, Connolly K, Duffey M, Durvasula N, Freeze S, Gallery M, Galvin K, Gaulin J, Gershman R, Greenspan P, Grieves J, Guo J, Gulavita N, Hailu S, He X, Hoar K, Hu Y, Hu Z, Ito M, Kim MS, Lane SW, Lok D, Lublinsky A, Mallender W, McIntyre C, Minissale J, Mizutani H, Mizutani M, Molchinova N, Ono K, Patil A, Qian M, Riceberg J, Shindi V, Sintchak MD, Song K, Soucy T, Wang Y, Xu H, Yang X, Zawadzka A, Zhang J, Pulukuri SM J Med Chem. 2021 Mar 11;64(5):2501-2520. doi: 10.1021/acs.jmedchem.0c01491. Epub , 2021 Feb 25. PMID:33631934<ref>PMID:33631934</ref>
-Description: Structure of SUMO1-ML00752641 adduct bound to SAE
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Bump, N]]
+<div class="pdbe-citations 6xoi" style="background-color:#fffaf0;"></div>
-[[Category: Lane, W]]
-[[Category: Sintchak, M]]
+==See Also==
+*[[SUMO 3D Structures|SUMO 3D Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bump N]]
+[[Category: Lane W]]
+[[Category: Sintchak M]]