OCA at 14:15, 29 December 2021

OCA — Wed, 29 Dec 2021 14:15:59 GMT

←Older revision		Revision as of 14:15, 29 December 2021
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	==Structure of XL5-ligated hRpn13 Pru domain==		==Structure of XL5-ligated hRpn13 Pru domain==
-	<StructureSection load='7kxi' size='340' side='right'caption='[[7kxi]]' scene=''>	+	<StructureSection load='7kxi' size='340' side='right'caption='[[7kxi]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' 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=7KXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KXI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kxi]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KXI 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=7kxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kxi OCA], [https://pdbe.org/7kxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kxi RCSB], [https://www.ebi.ac.uk/pdbsum/7kxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kxi ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XAY:2-{[(2S)-2-cyano-3-{3-[(4-methylbenzene-1-carbonyl)amino]phenyl}propanoyl]amino}benzoic+acid'>XAY</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=7kxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kxi OCA], [https://pdbe.org/7kxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kxi RCSB], [https://www.ebi.ac.uk/pdbsum/7kxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kxi ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/ADRM1_HUMAN ADRM1_HUMAN]] Functions as a proteasomal ubiquitin receptor. Recruits the deubiquitinating enzyme UCHL5 at the 26S proteasome and promotes its activity.<ref>PMID:16990800</ref> <ref>PMID:17139257</ref> <ref>PMID:16815440</ref> <ref>PMID:16906146</ref> <ref>PMID:18497817</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Proteasome substrate receptor hRpn13 is a promising anti-cancer target. By integrated in silico and biophysical screening, we identified a chemical scaffold that binds hRpn13 with non-covalent interactions that mimic the proteasome and a weak electrophile for Michael addition. hRpn13 Pru domain binds proteasomes and ubiquitin whereas its DEUBAD domain binds deubiquitinating enzyme UCHL5. NMR revealed lead compound XL5 to interdigitate into a hydrophobic pocket created by lateral movement of a Pru beta-hairpin with an exposed end for Proteolysis Targeting Chimeras (PROTACs). Implementing XL5-PROTACs as chemical probes identified a DEUBAD-lacking hRpn13 species (hRpn13(Pru)) present naturally with cell type-dependent abundance. XL5-PROTACs preferentially target hRpn13(Pru), causing its ubiquitination. Gene-editing and rescue experiments established hRpn13 requirement for XL5-PROTAC-triggered apoptosis. These data establish hRpn13 as an anti-cancer target for multiple myeloma and introduce an hRpn13-targeting scaffold that can be optimized for preclinical trials against hRpn13(Pru)-producing cancer types.
		+
		+	Structure-guided bifunctional molecules hit a DEUBAD-lacking hRpn13 species upregulated in multiple myeloma.,Lu X, Sabbasani VR, Osei-Amponsa V, Evans CN, King JC, Tarasov SG, Dyba M, Das S, Chan KC, Schwieters CD, Choudhari S, Fromont C, Zhao Y, Tran B, Chen X, Matsuo H, Andresson T, Chari R, Swenson RE, Tarasova NI, Walters KJ Nat Commun. 2021 Dec 16;12(1):7318. doi: 10.1038/s41467-021-27570-4. PMID:34916494<ref>PMID:34916494</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kxi" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Lu X]]	+	[[Category: Lu, X]]
-	[[Category: Walters KJ]]	+	[[Category: Walters, K J]]
		+	[[Category: Complex]]
		+	[[Category: Protein binding]]

OCA at 16:47, 15 December 2021

OCA — Wed, 15 Dec 2021 16:47:38 GMT

←Older revision		Revision as of 16:47, 15 December 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7kxi ~~is ON HOLD until Paper Publication~~	+	==Structure of XL5-ligated hRpn13 Pru domain==
-		+	<StructureSection load='7kxi' size='340' side='right'caption='[[7kxi]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KXI FirstGlance]. <br>
-	~~Description~~:	+	</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=7kxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kxi OCA], [https://pdbe.org/7kxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kxi RCSB], [https://www.ebi.ac.uk/pdbsum/7kxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kxi ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lu X]]
		+	[[Category: Walters KJ]]

OCA at 11:13, 16 December 2020

OCA — Wed, 16 Dec 2020 11:13:41 GMT

←Older revision		Revision as of 11:13, 16 December 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7kxi is ON HOLD	+	The entry 7kxi is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7kxi" [edit=sysop:move=sysop]

OCA — Wed, 09 Dec 2020 05:19:14 GMT

Protected "7kxi" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:19, 9 December 2020

OCA: New page: '''Unreleased structure''' The entry 7kxi is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 09 Dec 2020 05:19:13 GMT

New page: '''Unreleased structure''' The entry 7kxi is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7kxi is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7kxi - Revision history

OCA at 14:15, 29 December 2021

OCA at 16:47, 15 December 2021

OCA at 11:13, 16 December 2020

OCA: Protected "7kxi" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7kxi is ON HOLD Authors: Description: Category: Unreleased Structures