2o21: Difference between revisions

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-{{Seed}}
-[[Image:2o21.png|left|200px]]
-<!--
+==Solution structure of the anti-apoptotic protein Bcl-2 in complex with an acyl-sulfonamide-based ligand==
-The line below this paragraph, containing "STRUCTURE_2o21", creates the "Structure Box" on the page.
+<StructureSection load='2o21' size='340' side='right'caption='[[2o21]]' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2o21]] 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=2O21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O21 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=43B:3-NITRO-N-{4-[2-(2-PHENYLETHYL)-1,3-BENZOTHIAZOL-5-YL]BENZOYL}-4-{[2-(PHENYLSULFANYL)ETHYL]AMINO}BENZENESULFONAMIDE'>43B</scene></td></tr>
-{{STRUCTURE_2o21|  PDB=2o21  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2o21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o21 OCA], [https://pdbe.org/2o21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o21 RCSB], [https://www.ebi.ac.uk/pdbsum/2o21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o21 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[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 ==
+[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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o2/2o21_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=2o21 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-===Solution structure of the anti-apoptotic protein Bcl-2 in complex with an acyl-sulfonamide-based ligand===
+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>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2o21" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_17256834}}, adds the Publication Abstract to the page
+*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 17256834 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_17256834}}
+__TOC__
+</StructureSection>
-==Disease==
-Known disease associated with this structure: Leukemia/lymphoma, B-cell OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=151430 151430]]
-==About this Structure==
-O21 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=2O21 OCA].
-==Reference==
-<ref group="xtra">PMID:17256834</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Belli, B A.]]
+[[Category: Large Structures]]
-[[Category: Bruncko, M.]]
+[[Category: Belli BA]]
-[[Category: Ding, H.]]
+[[Category: Bruncko M]]
-[[Category: Elmore, S W.]]
+[[Category: Ding H]]
-[[Category: Fesik, S W.]]
+[[Category: Elmore SW]]
-[[Category: Joseph, M K.]]
+[[Category: Fesik SW]]
-[[Category: Kunzer, A.]]
+[[Category: Joseph MK]]
-[[Category: Martineau, D.]]
+[[Category: Kunzer A]]
-[[Category: McClellan, W J.]]
+[[Category: Martineau D]]
-[[Category: Mitten, M.]]
+[[Category: McClellan WJ]]
-[[Category: Ng, S C.]]
+[[Category: Mitten M]]
-[[Category: Nimmer, P M.]]
+[[Category: Ng SC]]
-[[Category: Oltersdorf, T.]]
+[[Category: Nimmer PM]]
-[[Category: Oost, T K.]]
+[[Category: Oltersdorf T]]
-[[Category: Park, C M.]]
+[[Category: Oost TK]]
-[[Category: Petros, A M.]]
+[[Category: Park CM]]
-[[Category: Rosenberg, S H.]]
+[[Category: Petros AM]]
-[[Category: Shoemaker, A R.]]
+[[Category: Rosenberg SH]]
-[[Category: Song, X.]]
+[[Category: Shoemaker AR]]
-[[Category: Wang, X.]]
+[[Category: Song X]]
-[[Category: Wendt, M D.]]
+[[Category: Wang X]]
-[[Category: Zhang, H.]]
+[[Category: Wendt MD]]
-[[Category: Apoptosis]]
+[[Category: Zhang H]]
-[[Category: Bcl]]
-[[Category: Complex]]
-[[Category: Nmr]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 21:56:45 2009''