6xoh - Revision history

OCA at 14:57, 18 October 2023

2023-10-18T14:57:43Z

←Older revision		Revision as of 14:57, 18 October 2023
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-	====	+	==Structure of SUMO1-ML00789344 adduct bound to SAE==
-	<StructureSection load='6xoh' size='340' side='right'caption='[[6xoh]]' scene=''>	+	<StructureSection load='6xoh' size='340' side='right'caption='[[6xoh]], [[Resolution\|resolution]] 2.23Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xoh]] 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=6XOH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XOH FirstGlance]. <br>
-	</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=6xoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xoh OCA], [https://pdbe.org/6xoh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xoh RCSB], [https://www.ebi.ac.uk/pdbsum/6xoh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xoh ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.226Å</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=VB7:{(1R,2S,4R)-4-[(5-{4-[(1R)-3,4-dihydro-1H-2-benzopyran-1-yl]thiophene-2-carbonyl}pyrimidin-4-yl)amino]-2-hydroxycyclopentyl}methyl+sulfamate'>VB7</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=6xoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xoh OCA], [https://pdbe.org/6xoh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xoh RCSB], [https://www.ebi.ac.uk/pdbsum/6xoh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xoh ProSAT]</span></td></tr>
	</table>		</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.
		+
		+	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>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6xoh" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[SUMO 3D Structures\|SUMO 3D Structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Bump N]]
		+	[[Category: Lane W]]
		+	[[Category: Sintchak M]]

OCA at 06:38, 24 March 2021

2021-03-24T06:38:16Z

←Older revision		Revision as of 06:38, 24 March 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 6xoh ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='6xoh' size='340' side='right'caption='[[6xoh]]' scene=''>
-	~~Authors~~: ~~Sintchak, M~~.~~, Lane, W~~.~~, Bump, N~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description: Structure of SUMO1~~-~~ML00789344 adduct bound to SAE~~	+	</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=6xoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xoh OCA], [https://pdbe.org/6xoh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xoh RCSB], [https://www.ebi.ac.uk/pdbsum/6xoh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xoh ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Sintchak~~, M]]	+	__TOC__
-	[[Category: ~~Bump, N~~]]	+	</StructureSection>
-	[[Category: ~~Lane, W~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 04:19, 7 October 2020

2020-10-07T04:19:57Z

←Older revision		Revision as of 04:19, 7 October 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6xoh is ON HOLD	+	The entry 6xoh is ON HOLD until Paper Publication

	Authors: Sintchak, M., Lane, W., Bump, N.		Authors: Sintchak, M., Lane, W., Bump, N.
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	Description: Structure of SUMO1-ML00789344 adduct bound to SAE		Description: Structure of SUMO1-ML00789344 adduct bound to SAE
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Sintchak, M]]
	[[Category: Bump, N]]		[[Category: Bump, N]]
	[[Category: Lane, W]]		[[Category: Lane, W]]
-	[[Category: Sintchak, M]]

OCA: Protected "6xoh" [edit=sysop:move=sysop]

2020-07-22T06:48:01Z

Protected "6xoh" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:48, 22 July 2020

OCA: New page: '''Unreleased structure''' The entry 6xoh is ON HOLD Authors: Sintchak, M., Lane, W., Bump, N. Description: Structure of SUMO1-ML00789344 adduct bound to SAE [[Category: Unreleased Str...

2020-07-22T06:48:00Z

New page: '''Unreleased structure''' The entry 6xoh is ON HOLD Authors: Sintchak, M., Lane, W., Bump, N. Description: Structure of SUMO1-ML00789344 adduct bound to SAE [[Category: Unreleased Str...

New page

'''Unreleased structure'''

The entry 6xoh is ON HOLD

Authors: Sintchak, M., Lane, W., Bump, N.

Description: Structure of SUMO1-ML00789344 adduct bound to SAE
[[Category: Unreleased Structures]]
[[Category: Bump, N]]
[[Category: Lane, W]]
[[Category: Sintchak, M]]