1ysw

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{{Seed}}
 
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[[Image:1ysw.png|left|200px]]
 
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==Solution structure of the anti-apoptotic protein Bcl-2 complexed with an acyl-sulfonamide-based ligand==
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The line below this paragraph, containing "STRUCTURE_1ysw", creates the "Structure Box" on the page.
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<StructureSection load='1ysw' size='340' side='right'caption='[[1ysw]]' 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'>[[1ysw]] 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=1YSW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YSW 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=43B:3-NITRO-N-{4-[2-(2-PHENYLETHYL)-1,3-BENZOTHIAZOL-5-YL]BENZOYL}-4-{[2-(PHENYLSULFANYL)ETHYL]AMINO}BENZENESULFONAMIDE'>43B</scene></td></tr>
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{{STRUCTURE_1ysw| PDB=1ysw | 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=1ysw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ysw OCA], [https://pdbe.org/1ysw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ysw RCSB], [https://www.ebi.ac.uk/pdbsum/1ysw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ysw 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/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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== 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/ys/1ysw_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=1ysw 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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Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice.
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===Solution structure of the anti-apoptotic protein Bcl-2 complexed with an acyl-sulfonamide-based ligand===
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An inhibitor of Bcl-2 family proteins induces regression of solid tumours.,Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O'Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH Nature. 2005 Jun 2;435(7042):677-81. Epub 2005 May 15. PMID:15902208<ref>PMID:15902208</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 1ysw" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15902208}}, 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 15902208 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15902208}}
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: Leukemia/lymphoma, B-cell OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=151430 151430]]
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==About this Structure==
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1YSW 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=1YSW OCA].
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==Reference==
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<ref group="xtra">PMID:15902208</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Armstrong, R C.]]
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[[Category: Large Structures]]
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[[Category: Augeri, D J.]]
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[[Category: Armstrong RC]]
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[[Category: Belli, B A.]]
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[[Category: Augeri DJ]]
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[[Category: Bruncko, M.]]
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[[Category: Belli BA]]
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[[Category: Connor, J M.O.]]
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[[Category: Bruncko M]]
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[[Category: Deckwerth, T L.]]
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[[Category: Deckwerth TL]]
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[[Category: Dinges, J.]]
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[[Category: Dinges J]]
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[[Category: Elmore, S W.]]
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[[Category: Elmore SW]]
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[[Category: Fesik, S W.]]
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[[Category: Fesik SW]]
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[[Category: Hajduk, P J.]]
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[[Category: Hajduk PJ]]
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[[Category: Joseph, M K.]]
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[[Category: Joseph MK]]
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[[Category: Kitada, S.]]
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[[Category: Kitada S]]
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[[Category: Korsmeyer, S J.]]
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[[Category: Korsmeyer SJ]]
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[[Category: Kunzer, A R.]]
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[[Category: Kunzer AR]]
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[[Category: Letai, A.]]
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[[Category: Letai A]]
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[[Category: Li, C.]]
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[[Category: Li C]]
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[[Category: Mitten, M J.]]
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[[Category: Mitten MJ]]
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[[Category: Nettesheim, D G.]]
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[[Category: Nettesheim DG]]
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[[Category: Ng, S.]]
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[[Category: Ng S]]
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[[Category: Nimmer, P M.]]
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[[Category: Nimmer PM]]
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[[Category: Oleksijew, A.]]
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[[Category: O'Connor JM]]
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[[Category: Oltersdorf, T.]]
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[[Category: Oleksijew A]]
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[[Category: Petros, A M.]]
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[[Category: Oltersdorf T]]
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[[Category: Reed, J C.]]
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[[Category: Petros AM]]
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[[Category: Rosenberg, S H.]]
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[[Category: Reed JC]]
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[[Category: Shen, W.]]
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[[Category: Rosenberg SH]]
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[[Category: Shoemaker, A R.]]
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[[Category: Shen W]]
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[[Category: Tahir, S K.]]
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[[Category: Shoemaker AR]]
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[[Category: Thompson, C B.]]
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[[Category: Tahir SK]]
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[[Category: Tomaselli, K J.]]
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[[Category: Thompson CB]]
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[[Category: Wang, B.]]
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[[Category: Tomaselli KJ]]
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[[Category: Wendt, M D.]]
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[[Category: Wang B]]
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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: Complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 18 18:21:10 2009''
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Current revision

Solution structure of the anti-apoptotic protein Bcl-2 complexed with an acyl-sulfonamide-based ligand

PDB ID 1ysw

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OCA

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