4ehr - Revision history

OCA at 11:03, 1 March 2024

2024-03-01T11:03:54Z

← Older revision		Revision as of 11:03, 1 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ehr]] 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=4EHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EHR FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ehr]] 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=4EHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EHR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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]] 2.09Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [https://pdbe.org/4ehr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [https://www.ebi.ac.uk/pdbsum/4ehr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehr 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=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [https://pdbe.org/4ehr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [https://www.ebi.ac.uk/pdbsum/4ehr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehr 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;">~~
	~~== Publication Abstract from PubMed ==~~
	5-Butyl-1,4-diphenyl pyrazole and 2-amino-5-chloro pyrimidine acylsulfonamides were developed as potent dual antagonists of Bcl-2 and Bcl-xL. Compounds were optimized for binding to the I88, L92, I95, and F99 pockets normally occupied by pro-apoptotic protein Bim. An X-ray crystal structure confirmed the proposed binding mode. Observation of cytochrome c release from isolated mitochondria in MV-411 cells provides further evidence of target inhibition. Compounds demonstrated submicromolar antiproliferative activity in Bcl-2/Bcl-xL dependent cell lines.

	Pyrazole and pyrimidine phenylacylsulfonamides as dual Bcl-2/Bcl-xL antagonists.,Schroeder GM, Wei D, Banfi P, Cai ZW, Lippy J, Menichincheri M, Modugno M, Naglich J, Penhallow B, Perez HL, Sack J, Schmidt RJ, Tebben A, Yan C, Zhang L, Galvani A, Lombardo LJ, Borzilleri RM Bioorg Med Chem Lett. 2012 Jun 15;22(12):3951-6. Epub 2012 Apr 30. PMID:22608393<ref>PMID:22608393</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4ehr" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==

OCA at 07:11, 28 September 2022

2022-09-28T07:11:57Z

← Older revision		Revision as of 07:11, 28 September 2022
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	==Crystal structure of Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide==		==Crystal structure of Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide==
	<StructureSection load='4ehr' size='340' side='right' caption='[[4ehr]], [[Resolution\|resolution]] 2.09Å' scene=''>		<StructureSection load='4ehr' size='340' side='right'caption='[[4ehr]], [[Resolution\|resolution]] 2.09Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ehr]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EHR FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ehr]] 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=4EHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EHR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>~~</td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2L1, BCL2L, BCLX ([http://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=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [https://pdbe.org/4ehr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [https://www.ebi.ac.uk/pdbsum/4ehr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehr ProSAT]</span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [~~http~~://pdbe.org/4ehr PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ehr PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://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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	</div>		</div>
	<div class="pdbe-citations 4ehr" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ehr" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[B-cell lymphoma proteins 3D structures\|B-cell lymphoma proteins 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Banfi, P]]		[[Category: Large Structures]]
	[[Category: Borzilleri~~, R M~~]]		[[Category: Banfi P]]
	[[Category: Cai, Z]]		[[Category: Borzilleri RM]]
	[[Category: Galvani, A]]		[[Category: Cai Z]]
	[[Category: Lippy, J]]		[[Category: Galvani A]]
	[[Category: Lombardo~~, L J~~]]		[[Category: Lippy J]]
	[[Category: Menichincheri, M]]		[[Category: Lombardo LJ]]
	[[Category: Modugno, M]]		[[Category: Menichincheri M]]
	[[Category: Naglich, J]]		[[Category: Modugno M]]
	[[Category: Penhallow, B]]		[[Category: Naglich J]]
	[[Category: Perez~~, H L~~]]		[[Category: Penhallow B]]
	[[Category: Sack, J]]		[[Category: Perez HL]]
	[[Category: Schmidt~~, R J~~]]		[[Category: Sack J]]
	[[Category: Schroeder~~, G M~~]]		[[Category: Schmidt RJ]]
	[[Category: Tebben, A]]		[[Category: Schroeder GM]]
	[[Category: Wei, D]]		[[Category: Tebben A]]
	[[Category: Yan, C]]		[[Category: Wei D]]
	[[Category: Zhang, L]]		[[Category: Yan C]]
	~~[[Category: Apoptosis]]~~		[[Category: Zhang L]]
	~~[[Category: Bcl-2 family]]~~
	~~[[Category: Programmed cell death~~]]

OCA at 02:46, 5 August 2016

2016-08-05T02:46:44Z

← Older revision		Revision as of 02:46, 5 August 2016
Line 1:		Line 1:

	==Crystal structure of Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide==		==Crystal structure of Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide==
	<StructureSection load='4ehr' size='340' side='right' caption='[[4ehr]], [[Resolution\|resolution]] 2.09Å' scene=''>		<StructureSection load='4ehr' size='340' side='right' caption='[[4ehr]], [[Resolution\|resolution]] 2.09Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ehr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHR FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ehr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2L1, BCL2L, BCLX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2L1, BCL2L, BCLX ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [http://www.ebi.ac.uk/pdbsum/4ehr PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [http://pdbe.org/4ehr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [http://www.ebi.ac.uk/pdbsum/4ehr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4ehr" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Banfi, P]]		[[Category: Banfi, P]]
	[[Category: Borzilleri, R M]]		[[Category: Borzilleri, R M]]

OCA at 22:09, 24 December 2014

2014-12-24T22:09:47Z

← Older revision		Revision as of 22:09, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ehr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHR FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ehr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHR FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2L1, BCL2L, BCLX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2L1, BCL2L, BCLX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [http://www.ebi.ac.uk/pdbsum/4ehr PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [http://www.ebi.ac.uk/pdbsum/4ehr PDBsum]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://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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	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Banfi, P.]]		[[Category: Banfi, P]]
	[[Category: Borzilleri, R M.]]		[[Category: Borzilleri, R M]]
	[[Category: Cai, Z.]]		[[Category: Cai, Z]]
	[[Category: Galvani, A.]]		[[Category: Galvani, A]]
	[[Category: Lippy, J.]]		[[Category: Lippy, J]]
	[[Category: Lombardo, L J.]]		[[Category: Lombardo, L J]]
	[[Category: Menichincheri, M.]]		[[Category: Menichincheri, M]]
	[[Category: Modugno, M.]]		[[Category: Modugno, M]]
	[[Category: Naglich, J.]]		[[Category: Naglich, J]]
	[[Category: Penhallow, B.]]		[[Category: Penhallow, B]]
	[[Category: Perez, H L.]]		[[Category: Perez, H L]]
	[[Category: Sack, J.]]		[[Category: Sack, J]]
	[[Category: Schmidt, R J.]]		[[Category: Schmidt, R J]]
	[[Category: Schroeder, G M.]]		[[Category: Schroeder, G M]]
	[[Category: Tebben, A.]]		[[Category: Tebben, A]]
	[[Category: Wei, D.]]		[[Category: Wei, D]]
	[[Category: Yan, C.]]		[[Category: Yan, C]]
	[[Category: Zhang, L.]]		[[Category: Zhang, L]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]
	[[Category: Bcl-2 family]]		[[Category: Bcl-2 family]]
	[[Category: Programmed cell death]]		[[Category: Programmed cell death]]

OCA at 07:31, 5 June 2014

2014-06-05T07:31:50Z

← Older revision		Revision as of 07:31, 5 June 2014
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	[[~~Image~~:~~4ehr~~.~~png~~\|~~left~~\|~~200px~~]]		==Crystal structure of Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide==
			<StructureSection load='4ehr' size='340' side='right' caption='[[4ehr]], [[Resolution\|resolution]] 2.09Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4ehr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHR FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0Q5:4-[5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL]-3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLCARBONYL)-N-{[2-(TRIMETHYLSILYL)ETHYL]SULFONYL}BENZAMIDE'>0Q5</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene><br>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2L1, BCL2L, BCLX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ehr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ehr RCSB], [http://www.ebi.ac.uk/pdbsum/4ehr PDBsum]</span></td></tr>
			<table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			5-Butyl-1,4-diphenyl pyrazole and 2-amino-5-chloro pyrimidine acylsulfonamides were developed as potent dual antagonists of Bcl-2 and Bcl-xL. Compounds were optimized for binding to the I88, L92, I95, and F99 pockets normally occupied by pro-apoptotic protein Bim. An X-ray crystal structure confirmed the proposed binding mode. Observation of cytochrome c release from isolated mitochondria in MV-411 cells provides further evidence of target inhibition. Compounds demonstrated submicromolar antiproliferative activity in Bcl-2/Bcl-xL dependent cell lines.

	<!--		Pyrazole and pyrimidine phenylacylsulfonamides as dual Bcl-2/Bcl-xL antagonists.,Schroeder GM, Wei D, Banfi P, Cai ZW, Lippy J, Menichincheri M, Modugno M, Naglich J, Penhallow B, Perez HL, Sack J, Schmidt RJ, Tebben A, Yan C, Zhang L, Galvani A, Lombardo LJ, Borzilleri RM Bioorg Med Chem Lett. 2012 Jun 15;22(12):3951-6. Epub 2012 Apr 30. PMID:22608393<ref>PMID:22608393</ref>
	~~The line below this paragraph~~, ~~containing "STRUCTURE_4ehr"~~, ~~creates the "Structure Box" on the page~~.
	~~You may change the PDB parameter~~ (~~which sets the PDB file loaded into the applet~~)
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display~~.
	-->
	~~{{STRUCTURE_4ehr\| PDB=4ehr \| SCENE= }}~~

	~~===Crystal structure~~ of ~~Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			== References ==
	~~<!--~~		<references/>
	~~The line below this paragraph, {{ABSTRACT_PUBMED_22608393}}, adds the Publication Abstract to~~ the ~~page~~		__TOC__
	~~(as it appears on PubMed at http://www~~.~~pubmed~~.~~gov), where 22608393 is the PubMed ID number~~.		</StructureSection>
	-->
	~~{{ABSTRACT_PUBMED_22608393}}~~

	~~==About this Structure==~~
	~~[[4ehr]] is a 1 chain structure with sequence from [http:~~/~~/en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHR OCA].~~

	==~~Reference~~==
	<~~ref group="xtra">PMID:022608393<~~/~~ref~~><~~references group="xtra"~~/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Banfi, P.]]		[[Category: Banfi, P.]]

OCA at 05:22, 13 June 2012

2012-06-13T05:22:40Z

← Older revision		Revision as of 05:22, 13 June 2012
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	[[Image:4ehr.~~jpg~~\|left\|200px]]		[[Image:4ehr.png\|left\|200px]]

	<!--		<!--

OCA at 07:44, 6 June 2012

2012-06-06T07:44:36Z

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-'''Unreleased structure'''
+[[Image:4ehr.jpg|left|200px]]
-The entry 4ehr is ON HOLD  until Paper Publication
+<!--
-Authors: Schroeder, G.M., Wei, D., Banfi, P., Cai, Z., Lippy, J., Menichincheri, M., Modugno, M., Naglich, J., Penhallow, B., Perez, H.L., Sack, J., Schmidt, R.J., Tebben, A., Yan, C., Zhang, L., Galvani, A., Lombardo, L.J., Borzilleri, R.M.
+===Crystal structure of Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide===
-Description: Crystal structure of Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide

OCA at 07:31, 18 April 2012

2012-04-18T07:31:43Z

← Older revision		Revision as of 07:31, 18 April 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4ehr is ON HOLD		The entry 4ehr is ON HOLD until Paper Publication

	Authors: Schroeder, G.M., Wei, D., Banfi, P., Cai, Z., Lippy, J., Menichincheri, M., Modugno, M., Naglich, J., Penhallow, B., Perez, H.L., Sack, J., Schmidt, R.J., Tebben, A., Yan, C., Zhang, L., Galvani, A., Lombardo, L.J., Borzilleri, R.M.		Authors: Schroeder, G.M., Wei, D., Banfi, P., Cai, Z., Lippy, J., Menichincheri, M., Modugno, M., Naglich, J., Penhallow, B., Perez, H.L., Sack, J., Schmidt, R.J., Tebben, A., Yan, C., Zhang, L., Galvani, A., Lombardo, L.J., Borzilleri, R.M.

	Description: ~~CRYSTAL STRUCTURE OF BCL~~-~~XL COMPLEX WITH~~ 4-(5-~~BUTYL~~-3-(~~HYDROXYMETHYL~~)-1-~~PHENYL~~-1H-~~PYRAZOL~~-4-YL)-3-(3,4-~~DIHYDRO~~-2(1H)-~~ISOQUINOLINYLCARBONYL~~)-N-((2-(~~TRIMETHYLSILYL~~)~~ETHYL~~)~~SULFONYL~~)~~BENZAMIDE~~		Description: Crystal structure of Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide

OCA: Protected "4ehr" [edit=sysop:move=sysop]

2012-04-11T06:43:36Z

Protected "4ehr" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:43, 11 April 2012
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4ehr is ON HOLD Authors: Schroeder, G.M., Wei, D., Banfi, P., Cai, Z., Lippy, J., Menichincheri, M., Modugno, M., Naglich, J., Penhallow, B., Perez,...

2012-04-11T06:43:35Z

New page: '''Unreleased structure''' The entry 4ehr is ON HOLD Authors: Schroeder, G.M., Wei, D., Banfi, P., Cai, Z., Lippy, J., Menichincheri, M., Modugno, M., Naglich, J., Penhallow, B., Perez,...

New page

'''Unreleased structure'''

The entry 4ehr is ON HOLD

Authors: Schroeder, G.M., Wei, D., Banfi, P., Cai, Z., Lippy, J., Menichincheri, M., Modugno, M., Naglich, J., Penhallow, B., Perez, H.L., Sack, J., Schmidt, R.J., Tebben, A., Yan, C., Zhang, L., Galvani, A., Lombardo, L.J., Borzilleri, R.M.

Description: CRYSTAL STRUCTURE OF BCL-XL COMPLEX WITH 4-(5-BUTYL-3-(HYDROXYMETHYL)-1-PHENYL-1H-PYRAZOL-4-YL)-3-(3,4-DIHYDRO-2(1H)-ISOQUINOLINYLCARBONYL)-N-((2-(TRIMETHYLSILYL)ETHYL)SULFONYL)BENZAMIDE