4ieh - Revision history

OCA at 11:54, 1 March 2024

OCA — Fri, 01 Mar 2024 11:54:53 GMT

←Older revision		Revision as of 11:54, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ieh]] 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=4IEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IEH FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ieh]] 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=4IEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IEH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1E9:N-(6-{4-[(4-CHLOROBIPHENYL-2-YL)METHYL]PIPERAZIN-1-YL}-1,1-DIOXIDO-1,2-BENZOTHIAZOL-3-YL)-4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL)BUTAN-2-YL]AMINO}-3-NITROBENZENESULFONAMIDE'>1E9</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]] 2.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1E9:N-(6-{4-[(4-CHLOROBIPHENYL-2-YL)METHYL]PIPERAZIN-1-YL}-1,1-DIOXIDO-1,2-BENZOTHIAZOL-3-YL)-4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL)BUTAN-2-YL]AMINO}-3-NITROBENZENESULFONAMIDE'>1E9</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=4ieh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ieh OCA], [https://pdbe.org/4ieh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ieh RCSB], [https://www.ebi.ac.uk/pdbsum/4ieh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ieh 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=4ieh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ieh OCA], [https://pdbe.org/4ieh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ieh RCSB], [https://www.ebi.ac.uk/pdbsum/4ieh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ieh ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== 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/BCL2_HUMAN BCL2_HUMAN] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</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> [https://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.
-
-	The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.,Toure BB, Miller-Moslin K, Yusuff N, Perez L, Dore M, Joud C, Michael W, DiPietro L, van der Plas S, McEwan M, Lenoir F, Hoe M, Karki R, Springer C, Sullivan J, Levine K, Fiorilla C, Xie X, Kulathila R, Herlihy K, Porter D, Visser M ACS Med Chem Lett. 2013 Jan 4;4(2):186-90. doi: 10.1021/ml300321d. eCollection, 2013 Feb 14. PMID:24900652<ref>PMID:24900652</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4ieh" style="background-color:#fffaf0;"></div>

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

OCA at 09:04, 9 November 2022

OCA — Wed, 09 Nov 2022 09:04:50 GMT

←Older revision		Revision as of 09:04, 9 November 2022
Line 1:		Line 1:

	==Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions==		==Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions==
-	<StructureSection load='4ieh' size='340' side='right' caption='[[4ieh]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='4ieh' size='340' side='right'caption='[[4ieh]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ieh]] 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=4IEH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4IEH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ieh]] 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=4IEH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IEH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1E9:N-(6-{4-[(4-CHLOROBIPHENYL-2-YL)METHYL]PIPERAZIN-1-YL}-1,1-DIOXIDO-1,2-BENZOTHIAZOL-3-YL)-4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL)BUTAN-2-YL]AMINO}-3-NITROBENZENESULFONAMIDE'>1E9</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1E9:N-(6-{4-[(4-CHLOROBIPHENYL-2-YL)METHYL]PIPERAZIN-1-YL}-1,1-DIOXIDO-1,2-BENZOTHIAZOL-3-YL)-4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL)BUTAN-2-YL]AMINO}-3-NITROBENZENESULFONAMIDE'>1E9</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2, 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'>[https://proteopedia.org/fgij/fg.htm?mol=4ieh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ieh OCA], [https://pdbe.org/4ieh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ieh RCSB], [https://www.ebi.ac.uk/pdbsum/4ieh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ieh 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=4ieh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ieh OCA], [~~http~~://pdbe.org/4ieh PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ieh RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ieh PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ieh ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.	+	[https://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</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> [https://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4ieh" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ieh" 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: ~~Kulathila, R~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Xie, X~~]]	+	[[Category: Kulathila R]]
-	[[Category: ~~Alpha helical]]~~	+	[[Category: Xie X]]
-	~~[[Category: Apoptosis-inhibitor complex]]~~	+
-	~~[[Category: Bad]]~~	+
-	~~[[Category: Bak]]~~	+
-	~~[[Category: Bim]]~~	+
-	~~[[Category: Caspase activation]]~~	+
-	~~[[Category: Cytochrome c release]]~~	+
-	~~[[Category: Pro-apoptosis]]~~	+
-	~~[[Category: Protein-protein interaction]]~~	+
-	~~[[Category: Puma~~]]	+

OCA at 18:58, 11 August 2016

OCA — Thu, 11 Aug 2016 18:58:53 GMT

←Older revision		Revision as of 18:58, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions==		==Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions==
	<StructureSection load='4ieh' size='340' side='right' caption='[[4ieh]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='4ieh' size='340' side='right' caption='[[4ieh]], [[Resolution\|resolution]] 2.10Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1E9:N-(6-{4-[(4-CHLOROBIPHENYL-2-YL)METHYL]PIPERAZIN-1-YL}-1,1-DIOXIDO-1,2-BENZOTHIAZOL-3-YL)-4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL)BUTAN-2-YL]AMINO}-3-NITROBENZENESULFONAMIDE'>1E9</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1E9:N-(6-{4-[(4-CHLOROBIPHENYL-2-YL)METHYL]PIPERAZIN-1-YL}-1,1-DIOXIDO-1,2-BENZOTHIAZOL-3-YL)-4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL)BUTAN-2-YL]AMINO}-3-NITROBENZENESULFONAMIDE'>1E9</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2, BCL2L, BCL2L1, 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">BCL2, 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=4ieh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ieh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ieh RCSB], [http://www.ebi.ac.uk/pdbsum/4ieh 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=4ieh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ieh OCA], [http://pdbe.org/4ieh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ieh RCSB], [http://www.ebi.ac.uk/pdbsum/4ieh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ieh ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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 4ieh" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:18, 20 January 2015

OCA — Tue, 20 Jan 2015 09:18:00 GMT

←Older revision		Revision as of 09:18, 20 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ieh]] 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=4IEH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IEH FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ieh]] 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=4IEH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IEH FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1E9:N-(6-{4-[(4-CHLOROBIPHENYL-2-YL)METHYL]PIPERAZIN-1-YL}-1,1-DIOXIDO-1,2-BENZOTHIAZOL-3-YL)-4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL)BUTAN-2-YL]AMINO}-3-NITROBENZENESULFONAMIDE'>1E9</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1E9:N-(6-{4-[(4-CHLOROBIPHENYL-2-YL)METHYL]PIPERAZIN-1-YL}-1,1-DIOXIDO-1,2-BENZOTHIAZOL-3-YL)-4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL)BUTAN-2-YL]AMINO}-3-NITROBENZENESULFONAMIDE'>1E9</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2, BCL2L, BCL2L1, 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">BCL2, BCL2L, BCL2L1, BCLX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ieh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ieh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ieh RCSB], [http://www.ebi.ac.uk/pdbsum/4ieh 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=4ieh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ieh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ieh RCSB], [http://www.ebi.ac.uk/pdbsum/4ieh PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.		[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
Line 24:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Kulathila, R.]]	+	[[Category: Kulathila, R]]
-	[[Category: Xie, X.]]	+	[[Category: Xie, X]]
	[[Category: Alpha helical]]		[[Category: Alpha helical]]
	[[Category: Apoptosis-inhibitor complex]]		[[Category: Apoptosis-inhibitor complex]]

OCA at 06:12, 24 September 2014

OCA — Wed, 24 Sep 2014 06:12:06 GMT

←Older revision		Revision as of 06:12, 24 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4ieh\| PDB=4ieh \| SCENE= }}~~	+	==Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions==
-	===Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions===	+	<StructureSection load='4ieh' size='340' side='right' caption='[[4ieh]], [[Resolution\|resolution]] 2.10Å' scene=''>
-		+	== Structural highlights ==
-	==Disease==	+	<table><tr><td colspan='2'>[[4ieh]] 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=4IEH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IEH FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1E9:N-(6-{4-[(4-CHLOROBIPHENYL-2-YL)METHYL]PIPERAZIN-1-YL}-1,1-DIOXIDO-1,2-BENZOTHIAZOL-3-YL)-4-{[(2R)-4-(DIMETHYLAMINO)-1-(PHENYLSULFANYL)BUTAN-2-YL]AMINO}-3-NITROBENZENESULFONAMIDE'>1E9</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BCL2, BCL2L, BCL2L1, BCLX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ieh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ieh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ieh RCSB], [http://www.ebi.ac.uk/pdbsum/4ieh PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.		[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
-		+	== Function ==
-	==Function==	+
	[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>		[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.

-	~~==About this Structure==~~	+	The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.,Toure BB, Miller-Moslin K, Yusuff N, Perez L, Dore M, Joud C, Michael W, DiPietro L, van der Plas S, McEwan M, Lenoir F, Hoe M, Karki R, Springer C, Sullivan J, Levine K, Fiorilla C, Xie X, Kulathila R, Herlihy K, Porter D, Visser M ACS Med Chem Lett. 2013 Jan 4;4(2):186-90. doi: 10.1021/ml300321d. eCollection, 2013 Feb 14. PMID:24900652<ref>PMID:24900652</ref>
-	~~[[4ieh]] 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=4IEH OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	<references ~~group="xtra"~~/><~~references~~/>	+	</div>
-	[[Category: ~~Homo sapiens~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Kulathila, R.]]		[[Category: Kulathila, R.]]
	[[Category: Xie, X.]]		[[Category: Xie, X.]]

OCA at 15:52, 10 July 2013

OCA — Wed, 10 Jul 2013 15:52:49 GMT

←Older revision		Revision as of 15:52, 10 July 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4ieh\| PDB=4ieh \| SCENE= }}
		+	===Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions===

-	~~The entry 4ieh is ON HOLD until Paper Publication~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.

-	~~Authors~~: ~~Xie, X~~.~~, Kulathila, R~~.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN]] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>

-	~~Description: Crystal~~ Structure ~~of human Bcl-2 in complex with~~ a ~~small molecule~~ inhibitor ~~targeting Bcl~~-~~2 BH3 domain interactions~~	+	==About this Structure==
		+	[[4ieh]] 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=4IEH OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Kulathila, R.]]
		+	[[Category: Xie, X.]]
		+	[[Category: Alpha helical]]
		+	[[Category: Apoptosis-inhibitor complex]]
		+	[[Category: Bad]]
		+	[[Category: Bak]]
		+	[[Category: Bim]]
		+	[[Category: Caspase activation]]
		+	[[Category: Cytochrome c release]]
		+	[[Category: Pro-apoptosis]]
		+	[[Category: Protein-protein interaction]]
		+	[[Category: Puma]]

OCA at 07:02, 2 May 2013

OCA — Thu, 02 May 2013 07:02:32 GMT

←Older revision		Revision as of 07:02, 2 May 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ieh is ON HOLD	+	The entry 4ieh is ON HOLD until Paper Publication

	Authors: Xie, X., Kulathila, R.		Authors: Xie, X., Kulathila, R.

	Description: Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions		Description: Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions

OCA at 08:56, 2 January 2013

OCA — Wed, 02 Jan 2013 08:56:00 GMT

←Older revision		Revision as of 08:56, 2 January 2013
Line 3:		Line 3:
	The entry 4ieh is ON HOLD		The entry 4ieh is ON HOLD

-	Authors: ~~xie~~, X., ~~kulathila~~, R.	+	Authors: Xie, X., Kulathila, R.

	Description: Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions		Description: Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions

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

OCA — Wed, 19 Dec 2012 11:09:17 GMT

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

←Older revision

Revision as of 11:09, 19 December 2012

OCA: New page: '''Unreleased structure''' The entry 4ieh is ON HOLD Authors: xie, X., kulathila, R. Description: Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting ...

OCA — Wed, 19 Dec 2012 11:09:16 GMT

New page: '''Unreleased structure''' The entry 4ieh is ON HOLD Authors: xie, X., kulathila, R. Description: Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting ...

New page

'''Unreleased structure'''

The entry 4ieh is ON HOLD

Authors: xie, X., kulathila, R.

Description: Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions