7jgv - Revision history

OCA at 15:02, 18 October 2023

OCA — Wed, 18 Oct 2023 15:02:35 GMT

←Older revision		Revision as of 15:02, 18 October 2023
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	<StructureSection load='7jgv' size='340' side='right'caption='[[7jgv]], [[Resolution\|resolution]] 2.05Å' scene=''>		<StructureSection load='7jgv' size='340' side='right'caption='[[7jgv]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7jgv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JGV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JGV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7jgv]] 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=7JGV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JGV FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V9S:6-[(8E)-8-{2-[4-(benzylcarbamoyl)-1,3-thiazol-2-yl]hydrazinylidene}-5,6,7,8-tetrahydronaphthalen-2-yl]-3-(2-phenylethoxy)pyridine-2-carboxylic+acid'>V9S</scene>~~</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]] 2.05Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2L1, BCL2L, BCLX ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V9S:6-[(8E)-8-{2-[4-(benzylcarbamoyl)-1,3-thiazol-2-yl]hydrazinylidene}-5,6,7,8-tetrahydronaphthalen-2-yl]-3-(2-phenylethoxy)pyridine-2-carboxylic+acid'>V9S</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=7jgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jgv OCA], [https://pdbe.org/7jgv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jgv RCSB], [https://www.ebi.ac.uk/pdbsum/7jgv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jgv ProSAT]</span></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=7jgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jgv OCA], [https://pdbe.org/7jgv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jgv RCSB], [https://www.ebi.ac.uk/pdbsum/7jgv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jgv ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/B2CL1_HUMAN B2CL1_HUMAN]] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref> Isoform Bcl-X(S) promotes apoptosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref>	+	[https://www.uniprot.org/uniprot/B2CL1_HUMAN B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref> Isoform Bcl-X(S) promotes apoptosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Fairlie~~, W D~~]]	+	[[Category: Fairlie WD]]
-	[[Category: Lee~~, E F~~]]	+	[[Category: Lee EF]]
-	[[Category: Lee, M]]	+	[[Category: Lee M]]
-	[[Category: Smith~~, B J]]~~	+	[[Category: Smith BJ]]
-	~~[[Category: Alternative splicing]]~~	+
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Mitochondrion]]~~	+
-	~~[[Category: Poptosis~~]]	+

OCA at 09:27, 26 May 2021

OCA — Wed, 26 May 2021 09:27:52 GMT

←Older revision		Revision as of 09:27, 26 May 2021
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	==CRYSTAL STRUCTURE OF BCL-XL IN COMPLEX WITH COMPOUND 1620116, CRYSTAL FORM 2==		==CRYSTAL STRUCTURE OF BCL-XL IN COMPLEX WITH COMPOUND 1620116, CRYSTAL FORM 2==
-	<StructureSection load='7jgv' size='340' side='right'caption='[[7jgv]]' scene=''>	+	<StructureSection load='7jgv' size='340' side='right'caption='[[7jgv]], [[Resolution\|resolution]] 2.05Å' 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=7JGV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JGV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7jgv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JGV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JGV 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=7jgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jgv OCA], [https://pdbe.org/7jgv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jgv RCSB], [https://www.ebi.ac.uk/pdbsum/7jgv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jgv 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=V9S:6-[(8E)-8-{2-[4-(benzylcarbamoyl)-1,3-thiazol-2-yl]hydrazinylidene}-5,6,7,8-tetrahydronaphthalen-2-yl]-3-(2-phenylethoxy)pyridine-2-carboxylic+acid'>V9S</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2L1, BCL2L, BCLX ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7jgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jgv OCA], [https://pdbe.org/7jgv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jgv RCSB], [https://www.ebi.ac.uk/pdbsum/7jgv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jgv ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/B2CL1_HUMAN B2CL1_HUMAN]] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref> Isoform Bcl-X(S) promotes apoptosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Limited therapeutic options are available for the treatment of human schistosomiasis caused by the parasitic Schistosoma flatworm. The B cell lymphoma-2 (BCL-2)-regulated apoptotic cell death pathway in schistosomes was recently characterized and shown to share similarities with the intrinsic apoptosis pathway in humans. Here, we exploit structural differences in the human and schistosome BCL-2 (sBCL-2) pro-survival proteins toward a novel treatment strategy for schistosomiasis. The benzothiazole hydrazone scaffold previously employed to target human BCL-XL was repurposed as a starting point to target sBCL-2. We utilized X-ray structural data to inform optimization and then applied a scaffold-hop strategy to identify the 5-carboxamide thiazole hydrazone scaffold (43) with potent sBCL-2 activity (IC50 30 nM). Human BCL-XL potency (IC50 13 nM) was inadvertently preserved during the optimization process. The lead analogues from this study exhibit on-target activity in model fibroblast cell lines dependent on either sBCL-2 or human BCL-XL for survival. Further optimization of the thiazole hydrazone class is required to exhibit activity in schistosomes and enhance the potential of this strategy for treating schistosomiasis.
		+
		+	Optimization of Benzothiazole and Thiazole Hydrazones as Inhibitors of Schistosome BCL-2.,Nguyen W, Lee EF, Evangelista M, Lee M, Harris TJ, Colman PM, Smith NA, Williams LB, Jarman KE, Lowes KN, Haeberli C, Keiser J, Smith BJ, Fairlie WD, Sleebs BE ACS Infect Dis. 2021 Feb 1. doi: 10.1021/acsinfecdis.0c00700. PMID:33523649<ref>PMID:33523649</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7jgv" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[B-cell lymphoma proteins 3D structures\|B-cell lymphoma proteins 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Fairlie WD]]	+	[[Category: Fairlie, W D]]
-	[[Category: Lee EF]]	+	[[Category: Lee, E F]]
-	[[Category: Lee M]]	+	[[Category: Lee, M]]
-	[[Category: Smith BJ]]	+	[[Category: Smith, B J]]
		+	[[Category: Alternative splicing]]
		+	[[Category: Apoptosis]]
		+	[[Category: Membrane]]
		+	[[Category: Mitochondrion]]
		+	[[Category: Poptosis]]

OCA at 06:40, 24 February 2021

OCA — Wed, 24 Feb 2021 06:40:29 GMT

←Older revision		Revision as of 06:40, 24 February 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7jgv is ~~ON HOLD until Paper Publication~~	+	==CRYSTAL STRUCTURE OF BCL-XL IN COMPLEX WITH COMPOUND 1620116, CRYSTAL FORM 2==
-		+	<StructureSection load='7jgv' size='340' side='right'caption='[[7jgv]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JGV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JGV 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=7jgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jgv OCA], [https://pdbe.org/7jgv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jgv RCSB], [https://www.ebi.ac.uk/pdbsum/7jgv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jgv ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Fairlie WD]]
		+	[[Category: Lee EF]]
		+	[[Category: Lee M]]
		+	[[Category: Smith BJ]]

OCA at 04:12, 5 August 2020

OCA — Wed, 05 Aug 2020 04:12:48 GMT

←Older revision		Revision as of 04:12, 5 August 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 29 Jul 2020 09:47:42 GMT

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

←Older revision

Revision as of 09:47, 29 July 2020

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

OCA — Wed, 29 Jul 2020 09:47:41 GMT

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

New page

'''Unreleased structure'''

The entry 7jgv is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]