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4ieh

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{{STRUCTURE_4ieh| PDB=4ieh | SCENE= }}
 
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===Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions===
 
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==Disease==
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==Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions==
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[[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.
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<StructureSection load='4ieh' size='340' side='right'caption='[[4ieh]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<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>
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<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>
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</table>
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== Disease ==
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[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.
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== Function ==
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[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>
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==Function==
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==See Also==
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[[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>
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*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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[[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].
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__TOC__
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</StructureSection>
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==Reference==
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<references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Kulathila, R.]]
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[[Category: Large Structures]]
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[[Category: Xie, X.]]
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[[Category: Kulathila R]]
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[[Category: Alpha helical]]
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[[Category: Xie X]]
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[[Category: Apoptosis-inhibitor complex]]
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[[Category: Bad]]
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[[Category: Bak]]
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[[Category: Bim]]
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[[Category: Caspase activation]]
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[[Category: Cytochrome c release]]
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[[Category: Pro-apoptosis]]
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[[Category: Protein-protein interaction]]
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[[Category: Puma]]
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Current revision

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

PDB ID 4ieh

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