OCA at 14:45, 29 November 2023

OCA — Wed, 29 Nov 2023 14:45:55 GMT

←Older revision		Revision as of 14:45, 29 November 2023
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	==HSP90 in complex with Debio0932==		==HSP90 in complex with Debio0932==
-	<StructureSection load='6lr9' size='340' side='right'caption='[[6lr9]]' scene=''>	+	<StructureSection load='6lr9' size='340' side='right'caption='[[6lr9]], [[Resolution\|resolution]] 2.20Å' 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=6LR9 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6LR9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6lr9]] is a 1 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=6LR9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LR9 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6lr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lr9 OCA], [~~http~~://pdbe.org/6lr9 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6lr9 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6lr9 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6lr9 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]] 2.196Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EOR:2-[[6-(dimethylamino)-1,3-benzodioxol-5-yl]sulfanyl]-1-[2-(2,2-dimethylpropylamino)ethyl]imidazo[4,5-c]pyridin-4-amine'>EOR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6lr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lr9 OCA], [https://pdbe.org/6lr9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lr9 RCSB], [https://www.ebi.ac.uk/pdbsum/6lr9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lr9 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Debio0932 is a promising lead compound in phase I clinical trials targeting the N-terminal ATP-binding pocket of the molecular chaperone heat-shock protein 90 (Hsp90(N)). The absence of a crystal structure of the Hsp90(N)-Debio0932 complex, however, has impeded further structural optimization of Debio0932 and understanding of the molecular-interaction mechanism. Here, a high-resolution crystal structure of the Hsp90(N)-Debio0932 complex was successfully determined (resolution limit 2.20 A; PDB entry 6lr9) by X-ray diffraction and the molecular-interaction mechanism was analysed in detail, which suggested that Debio0932 suppresses cancer cells by accommodating itself in the ATP-binding pocket of Hsp90(N), disabling its molecular-chaperone capability. The results of a thermal shift assay (DeltaTm = 8.83 +/- 0.90 degrees C) and isothermal titration calorimetry (Kd = 15.50 +/- 1.30 nM) indicated strong binding and favourable thermodynamic changes in the binding of Hsp90(N) and Debio0932. Based on the crystal structure of the complex and on molecular-interaction analysis, 30 new Debio0932 derivatives were designed and nine new derivatives exhibited increased binding to Hsp90(N), as determined by molecular-docking evaluation. Additionally, Debio0932 suppressed cell proliferation (IC50 values of 3.26 +/- 2.82 microM for A549, 20.33 +/- 5.39 microM for H1299 and 3.16 +/- 1.04 microM for H1975), induced cell-cycle arrest and promoted apoptosis in three non-small-cell lung cancer (NSCLC) cell lines. These results provide novel perspectives and guidance for the development of new anti-NSCLC drugs based on the lead compound Debio0932.
		+
		+	Complex crystal structure determination and anti-non-small-cell lung cancer activity of the Hsp90(N) inhibitor Debio0932.,Qin W, Yu F, Zhou H, Li P, Zhou F, Li HJ, He CX, Xing L, Zhou X, Zhao D, Li PQ, Jin X, Wang QS, He JH, Cao HL Acta Crystallogr D Struct Biol. 2021 Jan 1;77(Pt 1):86-97. doi:, 10.1107/S2059798320014990. Epub 2021 Jan 1. PMID:33404528<ref>PMID:33404528</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6lr9" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Heat Shock Protein structures\|Heat Shock Protein structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Cao HL]]		[[Category: Cao HL]]

OCA at 05:46, 20 January 2021

OCA — Wed, 20 Jan 2021 05:46:57 GMT

←Older revision		Revision as of 05:46, 20 January 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 6lr9 ~~is ON HOLD until Paper Publication~~	+	==HSP90 in complex with Debio0932==
-		+	<StructureSection load='6lr9' size='340' side='right'caption='[[6lr9]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LR9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LR9 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lr9 OCA], [http://pdbe.org/6lr9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lr9 RCSB], [http://www.ebi.ac.uk/pdbsum/6lr9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lr9 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Cao HL]]

OCA at 13:03, 29 January 2020

OCA — Wed, 29 Jan 2020 13:03:16 GMT

←Older revision		Revision as of 13:03, 29 January 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6lr9 is ON HOLD	+	The entry 6lr9 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6lr9" [edit=sysop:move=sysop]

OCA — Wed, 22 Jan 2020 13:43:23 GMT

Protected "6lr9" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:43, 22 January 2020

OCA: New page: '''Unreleased structure''' The entry 6lr9 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 22 Jan 2020 13:43:22 GMT

New page: '''Unreleased structure''' The entry 6lr9 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6lr9 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

6lr9 - Revision history

OCA at 14:45, 29 November 2023

OCA at 05:46, 20 January 2021

OCA at 13:03, 29 January 2020

OCA: Protected "6lr9" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6lr9 is ON HOLD Authors: Description: Category: Unreleased Structures