OCA at 08:15, 16 August 2023

OCA — Wed, 16 Aug 2023 08:15:32 GMT

←Older revision		Revision as of 08:15, 16 August 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7u8u is ~~ON HOLD until Paper~~ Publication	+	==hTRAP1 with inhibitors==
		+	<StructureSection load='7u8u' size='340' side='right'caption='[[7u8u]], [[Resolution\|resolution]] 3.06Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7u8u]] 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=7U8U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U8U 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]] 3.065Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UJY:[2-hydroxy-5-(2H-isoindole-2-carbonyl)phenyl]{5-[3-(triphenyl-lambda~5~-phosphanyl)propoxy]-2H-isoindol-2-yl}methanone'>UJY</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=7u8u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u8u OCA], [https://pdbe.org/7u8u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u8u RCSB], [https://www.ebi.ac.uk/pdbsum/7u8u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u8u ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/TRAP1_HUMAN TRAP1_HUMAN] Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, most likely through stabilization of mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA.<ref>PMID:23525905</ref> <ref>PMID:23564345</ref> <ref>PMID:23747254</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Hsp90 isoform-selective inhibitors represent a new paradigm for novel anti-cancer drugs as each of the four isoforms have specific cellular localization, function, and client proteins. The mitochondrial isoform, TRAP1, is the least understood member of the Hsp90 family due to the lack of small molecule tools to study its biological function. Herein, we report novel TRAP1-selective inhibitors used to interrogate TRAP1's biological function along with co-crystal structures of such compounds bound to the N-terminus of TRAP1. Solution of the co-crystal structure allowed for a structure-based approach that resulted in compound 36, which is a 40 nM inhibitor with >250-fold TRAP1 selectivity over Grp94, the isoform with the highest structural similarity to TRAP1 within the N-terminal ATP binding site. Lead compounds 35 and 36 were found to selectively induce TRAP1 client protein degradation without inducing the heat shock response or disrupting Hsp90-cytosolic clients. They were also shown to inhibit OXPHOS, alter cellular metabolism towards glycolysis, disrupt TRAP1 tetramer stability, and disrupt the mitochondrial membrane potential.

-	~~Authors: Deng~~, J., Matts, R., ~~Peng, S~~.	+	Elucidation of novel TRAP1-Selective inhibitors that regulate mitochondrial processes.,Merfeld T, Peng S, Keegan BM, Crowley VM, Brackett CM, Gutierrez A, McCann NR, Reynolds TS, Rhodes MC, Byrd KM, Deng J, Matts RL, Blagg BSJ Eur J Med Chem. 2023 Oct 5;258:115531. doi: 10.1016/j.ejmech.2023.115531. Epub , 2023 Jun 5. PMID:37307624<ref>PMID:37307624</ref>

-	~~Description~~: ~~hTRAP1 with inhibitors~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Matts, R~~]]	+	<div class="pdbe-citations 7u8u" style="background-color:#fffaf0;"></div>
-	[[Category: Deng, J]]	+	== References ==
-	[[Category: Peng, S]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Deng J]]
		+	[[Category: Matts R]]
		+	[[Category: Peng S]]

OCA at 09:48, 23 March 2022

OCA — Wed, 23 Mar 2022 09:48:21 GMT

←Older revision		Revision as of 09:48, 23 March 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7u8u is ON HOLD	+	The entry 7u8u is ON HOLD until Paper Publication

	Authors: Deng, J., Matts, R., Peng, S.		Authors: Deng, J., Matts, R., Peng, S.
Line 7:		Line 7:
	Description: hTRAP1 with inhibitors		Description: hTRAP1 with inhibitors
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Matts, R]]
	[[Category: Deng, J]]		[[Category: Deng, J]]
	[[Category: Peng, S]]		[[Category: Peng, S]]
-	[[Category: Matts, R]]

OCA: Protected "7u8u" [edit=sysop:move=sysop]

OCA — Wed, 16 Mar 2022 05:06:01 GMT

Protected "7u8u" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:06, 16 March 2022

OCA: New page: '''Unreleased structure''' The entry 7u8u is ON HOLD Authors: Deng, J., Matts, R., Peng, S. Description: hTRAP1 with inhibitors Category: Unreleased Structures [[Category: Deng, J]...

OCA — Wed, 16 Mar 2022 05:05:59 GMT

New page: '''Unreleased structure''' The entry 7u8u is ON HOLD Authors: Deng, J., Matts, R., Peng, S. Description: hTRAP1 with inhibitors Category: Unreleased Structures [[Category: Deng, J]...

New page

'''Unreleased structure'''

The entry 7u8u is ON HOLD

Authors: Deng, J., Matts, R., Peng, S.

Description: hTRAP1 with inhibitors
[[Category: Unreleased Structures]]
[[Category: Deng, J]]
[[Category: Peng, S]]
[[Category: Matts, R]]

7u8u - Revision history

OCA at 08:15, 16 August 2023

OCA at 09:48, 23 March 2022

OCA: Protected "7u8u" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7u8u is ON HOLD Authors: Deng, J., Matts, R., Peng, S. Description: hTRAP1 with inhibitors Category: Unreleased Structures [[Category: Deng, J]...