3spf - Revision history

OCA at 09:54, 1 March 2024

OCA — Fri, 01 Mar 2024 09:54:13 GMT

←Older revision		Revision as of 09:54, 1 March 2024
Line 3:		Line 3:
	<StructureSection load='3spf' size='340' side='right'caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='3spf' size='340' side='right'caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3spf]] is a 1 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SPF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3spf]] 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SPF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.7Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3sp7\|3sp7]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [https://pdbe.org/3spf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [https://www.ebi.ac.uk/pdbsum/3spf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf 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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [https://pdbe.org/3spf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [https://www.ebi.ac.uk/pdbsum/3spf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf 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 ==~~	+
-	Employing a structure-based strategy, we have designed a new class of potent small-molecule inhibitors of the anti-apoptotic proteins Bcl-2 and Bcl-xL. An initial lead compound with a new scaffold was designed based upon the crystal structure of Bcl-xL and U.S. Food and Drug Administration (FDA) approved drugs and was found to have an affinity of 100 muM for both Bcl-2 and Bcl-xL. Linking this weak lead to another weak-affinity fragment derived from Abbott's ABT-737 led to an improvement of the binding affinity by a factor of >10 000. Further optimization ultimately yielded compounds with subnanomolar binding affinities for both Bcl-2 and Bcl-xL and potent cellular activity. The best compound (21) binds to Bcl-xL and Bcl-2 with K(i) < 1 nM, inhibits cell growth in the H146 and H1417 small-cell lung cancer cell lines with IC(50) values of 60-90 nM, and induces robust cell death in the H146 cancer cell line at 30-100 nM.	+
-		+
-	Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold.,Zhou H, Chen J, Meagher JL, Yang CY, Aguilar A, Liu L, Bai L, Cong X, Cai Q, Fang X, Stuckey JA, Wang S J Med Chem. 2012 May 24;55(10):4664-82. Epub 2012 May 10. PMID:22448988<ref>PMID:22448988</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3spf" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Meagher~~, J L~~]]	+	[[Category: Meagher JL]]
-	[[Category: Stuckey~~, J A]]~~	+	[[Category: Stuckey JA]]
-	~~[[Category: Apoptosis regulator-inhibitor complex]]~~	+
-	~~[[Category: Apoptosis-apoptosis inhibitor complex]]~~	+
-	~~[[Category: Bcl-2-like protein~~]]	+

OCA at 08:04, 29 June 2022

OCA — Wed, 29 Jun 2022 08:04:59 GMT

←Older revision		Revision as of 08:04, 29 June 2022
Line 1:		Line 1:

	==Crystal Structure of Bcl-xL bound to BM501==		==Crystal Structure of Bcl-xL bound to BM501==
-	<StructureSection load='3spf' size='340' side='right' caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>	+	<StructureSection load='3spf' size='340' side='right'caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3spf]] 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3SPF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3spf]] is a 1 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SPF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3sp7\|3sp7]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3sp7\|3sp7]]</div></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='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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [~~http~~://pdbe.org/3spf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3spf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf 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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [https://pdbe.org/3spf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [https://www.ebi.ac.uk/pdbsum/3spf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf 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 ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 3spf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3spf" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[B-cell lymphoma proteins 3D structures\|B-cell lymphoma proteins 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Meagher, J L]]		[[Category: Meagher, J L]]
	[[Category: Stuckey, J A]]		[[Category: Stuckey, J A]]

OCA at 09:40, 8 November 2017

OCA — Wed, 08 Nov 2017 09:40:52 GMT

←Older revision		Revision as of 09:40, 8 November 2017
Line 3:		Line 3:
	<StructureSection load='3spf' size='340' side='right' caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='3spf' size='340' side='right' caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3spf]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SPF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3spf]] 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SPF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3sp7\|3sp7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3sp7\|3sp7]]</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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [http://pdbe.org/3spf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [http://www.ebi.ac.uk/pdbsum/3spf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf 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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [http://pdbe.org/3spf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [http://www.ebi.ac.uk/pdbsum/3spf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Meagher, J L]]		[[Category: Meagher, J L]]
	[[Category: Stuckey, J A]]		[[Category: Stuckey, J A]]

OCA at 10:53, 3 August 2017

OCA — Thu, 03 Aug 2017 10:53:56 GMT

←Older revision		Revision as of 10:53, 3 August 2017
Line 3:		Line 3:
	<StructureSection load='3spf' size='340' side='right' caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='3spf' size='340' side='right' caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3spf]] 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SPF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3spf]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SPF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3sp7\|3sp7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3sp7\|3sp7]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Bcl-xL, BCL2L, BCL2L1, 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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [http://pdbe.org/3spf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [http://www.ebi.ac.uk/pdbsum/3spf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf 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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [http://pdbe.org/3spf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [http://www.ebi.ac.uk/pdbsum/3spf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human]]
	[[Category: Meagher, J L]]		[[Category: Meagher, J L]]
	[[Category: Stuckey, J A]]		[[Category: Stuckey, J A]]

OCA at 16:04, 4 August 2016

OCA — Thu, 04 Aug 2016 16:04:04 GMT

←Older revision		Revision as of 16:04, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of Bcl-xL bound to BM501==		==Crystal Structure of Bcl-xL bound to BM501==
	<StructureSection load='3spf' size='340' side='right' caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='3spf' size='340' side='right' caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3spf]] 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SPF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3spf]] 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SPF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3sp7\|3sp7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3sp7\|3sp7]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Bcl-xL, BCL2L, BCL2L1, 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">Bcl-xL, BCL2L, BCL2L1, 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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [http://www.ebi.ac.uk/pdbsum/3spf 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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [http://pdbe.org/3spf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [http://www.ebi.ac.uk/pdbsum/3spf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3spf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 3spf" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Meagher, J L]]		[[Category: Meagher, J L]]
	[[Category: Stuckey, J A]]		[[Category: Stuckey, J A]]

OCA at 10:51, 25 December 2014

OCA — Thu, 25 Dec 2014 10:51:42 GMT

←Older revision		Revision as of 10:51, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3spf]] 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SPF FirstGlance]. <br>		<table><tr><td colspan='2'>[[3spf]] 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SPF FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3sp7\|3sp7]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3sp7\|3sp7]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Bcl-xL, BCL2L, BCL2L1, 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">Bcl-xL, BCL2L, BCL2L1, 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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [http://www.ebi.ac.uk/pdbsum/3spf 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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [http://www.ebi.ac.uk/pdbsum/3spf 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 ==
Line 14:		Line 16:
	Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold.,Zhou H, Chen J, Meagher JL, Yang CY, Aguilar A, Liu L, Bai L, Cong X, Cai Q, Fang X, Stuckey JA, Wang S J Med Chem. 2012 May 24;55(10):4664-82. Epub 2012 May 10. PMID:22448988<ref>PMID:22448988</ref>		Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold.,Zhou H, Chen J, Meagher JL, Yang CY, Aguilar A, Liu L, Bai L, Cong X, Cai Q, Fang X, Stuckey JA, Wang S J Med Chem. 2012 May 24;55(10):4664-82. Epub 2012 May 10. PMID:22448988<ref>PMID:22448988</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
	== References ==		== References ==
Line 21:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Meagher, J L.]]	+	[[Category: Meagher, J L]]
-	[[Category: Stuckey, J A.]]	+	[[Category: Stuckey, J A]]
	[[Category: Apoptosis regulator-inhibitor complex]]		[[Category: Apoptosis regulator-inhibitor complex]]
	[[Category: Apoptosis-apoptosis inhibitor complex]]		[[Category: Apoptosis-apoptosis inhibitor complex]]
	[[Category: Bcl-2-like protein]]		[[Category: Bcl-2-like protein]]

OCA at 05:29, 5 June 2014

OCA — Thu, 05 Jun 2014 05:29:51 GMT

←Older revision		Revision as of 05:29, 5 June 2014
Line 1:		Line 1:
-	[[~~Image:~~3spf.~~jpg~~\|~~left~~\|~~200px~~]]	+	==Crystal Structure of Bcl-xL bound to BM501==
		+	<StructureSection load='3spf' size='340' side='right' caption='[[3spf]], [[Resolution\|resolution]] 1.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3spf]] 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=3SPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SPF FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3sp7\|3sp7]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Bcl-xL, BCL2L, BCL2L1, 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=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [http://www.ebi.ac.uk/pdbsum/3spf PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Employing a structure-based strategy, we have designed a new class of potent small-molecule inhibitors of the anti-apoptotic proteins Bcl-2 and Bcl-xL. An initial lead compound with a new scaffold was designed based upon the crystal structure of Bcl-xL and U.S. Food and Drug Administration (FDA) approved drugs and was found to have an affinity of 100 muM for both Bcl-2 and Bcl-xL. Linking this weak lead to another weak-affinity fragment derived from Abbott's ABT-737 led to an improvement of the binding affinity by a factor of >10 000. Further optimization ultimately yielded compounds with subnanomolar binding affinities for both Bcl-2 and Bcl-xL and potent cellular activity. The best compound (21) binds to Bcl-xL and Bcl-2 with K(i) < 1 nM, inhibits cell growth in the H146 and H1417 small-cell lung cancer cell lines with IC(50) values of 60-90 nM, and induces robust cell death in the H146 cancer cell line at 30-100 nM.

-	~~{{STRUCTURE_3spf\| PDB=3spf \| SCENE= }}~~	+	Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold.,Zhou H, Chen J, Meagher JL, Yang CY, Aguilar A, Liu L, Bai L, Cong X, Cai Q, Fang X, Stuckey JA, Wang S J Med Chem. 2012 May 24;55(10):4664-82. Epub 2012 May 10. PMID:22448988<ref>PMID:22448988</ref>

-	~~===Crystal Structure~~ of ~~Bcl-xL bound to BM501===~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_22448988}}~~	+	== References ==
-		+	<references/>
-	~~==About this Structure==~~	+	__TOC__
-	~~[[3spf]] 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=3SPF OCA].~~	+	</StructureSection>
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:022448988<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Meagher, J L.]]		[[Category: Meagher, J L.]]

OCA at 05:49, 27 June 2012

OCA — Wed, 27 Jun 2012 05:49:13 GMT

←Older revision		Revision as of 05:49, 27 June 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3spf.jpg\|left\|200px]]

-	~~The entry~~ 3spf ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_3spf\| PDB=3spf \| SCENE= }}

-	~~Authors: Meagher, J.L., Stuckey, J.A.~~	+	===Crystal Structure of Bcl-xL bound to BM501===

-	~~Description: Crystal~~ Structure of Bcl-~~xL bound to BM501~~	+	{{ABSTRACT_PUBMED_22448988}}
		+
		+	==About this Structure==
		+	[[3spf]] 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=3SPF OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022448988</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Meagher, J L.]]
		+	[[Category: Stuckey, J A.]]
		+	[[Category: Apoptosis regulator-inhibitor complex]]
		+	[[Category: Apoptosis-apoptosis inhibitor complex]]
		+	[[Category: Bcl-2-like protein]]

OCA at 05:40, 27 July 2011

OCA — Wed, 27 Jul 2011 05:40:52 GMT

←Older revision		Revision as of 05:40, 27 July 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3spf is ON HOLD	+	The entry 3spf is ON HOLD until Paper Publication

	Authors: Meagher, J.L., Stuckey, J.A.		Authors: Meagher, J.L., Stuckey, J.A.

	Description: Crystal Structure of Bcl-xL bound to BM501		Description: Crystal Structure of Bcl-xL bound to BM501

OCA at 06:14, 20 July 2011

OCA — Wed, 20 Jul 2011 06:14:01 GMT

←Older revision		Revision as of 06:14, 20 July 2011
Line 3:		Line 3:
	The entry 3spf is ON HOLD		The entry 3spf is ON HOLD

-	Authors: Meagher, J.L.., Stuckey, J.A.	+	Authors: Meagher, J.L., Stuckey, J.A.

	Description: Crystal Structure of Bcl-xL bound to BM501		Description: Crystal Structure of Bcl-xL bound to BM501