2o2m

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{{Seed}}
 
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[[Image:2o2m.png|left|200px]]
 
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==Solution structure of the anti-apoptotic protein Bcl-xL in complex with an acyl-sulfonamide-based ligand==
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The line below this paragraph, containing "STRUCTURE_2o2m", creates the "Structure Box" on the page.
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<StructureSection load='2o2m' size='340' side='right'caption='[[2o2m]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2o2m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O2M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O2M FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=LI0:4-(4-BENZYL-4-METHOXYPIPERIDIN-1-YL)-N-[(4-{[1,1-DIMETHYL-2-(PHENYLTHIO)ETHYL]AMINO}-3-NITROPHENYL)SULFONYL]BENZAMIDE'>LI0</scene></td></tr>
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{{STRUCTURE_2o2m| PDB=2o2m | SCENE= }}
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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=2o2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o2m OCA], [https://pdbe.org/2o2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o2m RCSB], [https://www.ebi.ac.uk/pdbsum/2o2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o2m ProSAT]</span></td></tr>
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</table>
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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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o2/2o2m_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2o2m ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.
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===Solution structure of the anti-apoptotic protein Bcl-xL in complex with an acyl-sulfonamide-based ligand===
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Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL.,Bruncko M, Oost TK, Belli BA, Ding H, Joseph MK, Kunzer A, Martineau D, McClellan WJ, Mitten M, Ng SC, Nimmer PM, Oltersdorf T, Park CM, Petros AM, Shoemaker AR, Song X, Wang X, Wendt MD, Zhang H, Fesik SW, Rosenberg SH, Elmore SW J Med Chem. 2007 Feb 22;50(4):641-62. Epub 2007 Jan 26. PMID:17256834<ref>PMID:17256834</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2o2m" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17256834}}, adds the Publication Abstract to the page
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*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17256834 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17256834}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2O2M is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O2M OCA].
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==Reference==
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<ref group="xtra">PMID:17256834</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Belli, B A.]]
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[[Category: Large Structures]]
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[[Category: Bruncko, M.]]
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[[Category: Belli BA]]
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[[Category: Ding, H.]]
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[[Category: Bruncko M]]
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[[Category: Elmore, S W.]]
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[[Category: Ding H]]
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[[Category: Fesik, S W.]]
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[[Category: Elmore SW]]
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[[Category: Joseph, M K.]]
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[[Category: Fesik SW]]
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[[Category: Kunzer, A.]]
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[[Category: Joseph MK]]
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[[Category: Martineau, D.]]
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[[Category: Kunzer A]]
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[[Category: McClellan, W J.]]
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[[Category: Martineau D]]
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[[Category: Mitten, M.]]
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[[Category: McClellan WJ]]
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[[Category: Ng, S C.]]
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[[Category: Mitten M]]
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[[Category: Nimmer, P M.]]
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[[Category: Ng SC]]
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[[Category: Oltersdorf, T.]]
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[[Category: Nimmer PM]]
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[[Category: Oost, T K.]]
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[[Category: Oltersdorf T]]
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[[Category: Park, C M.]]
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[[Category: Oost TK]]
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[[Category: Petros, A M.]]
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[[Category: Park CM]]
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[[Category: Rosenberg, S H.]]
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[[Category: Petros AM]]
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[[Category: Shoemaker, A R.]]
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[[Category: Rosenberg SH]]
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[[Category: Song, X.]]
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[[Category: Shoemaker AR]]
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[[Category: Wang, X.]]
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[[Category: Song X]]
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[[Category: Wendt, M D.]]
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[[Category: Wang X]]
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[[Category: Zhang, H.]]
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[[Category: Wendt MD]]
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[[Category: Apoptosis]]
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[[Category: Zhang H]]
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[[Category: Bcl]]
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[[Category: Complex]]
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[[Category: Nmr]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 15:50:37 2009''
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Current revision

Solution structure of the anti-apoptotic protein Bcl-xL in complex with an acyl-sulfonamide-based ligand

PDB ID 2o2m

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