3d7v

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{{Seed}}
 
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[[Image:3d7v.png|left|200px]]
 
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==Crystal structure of Mcl-1 in complex with an Mcl-1 selective BH3 ligand==
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The line below this paragraph, containing "STRUCTURE_3d7v", creates the "Structure Box" on the page.
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<StructureSection load='3d7v' size='340' side='right'caption='[[3d7v]], [[Resolution|resolution]] 2.03&Aring;' 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'>[[3d7v]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D7V 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">X-ray diffraction, [[Resolution|Resolution]] 2.03&#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=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_3d7v| PDB=3d7v | 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=3d7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d7v OCA], [https://pdbe.org/3d7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d7v RCSB], [https://www.ebi.ac.uk/pdbsum/3d7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d7v ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/B2L11_HUMAN B2L11_HUMAN] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.<ref>PMID:9430630</ref> <ref>PMID:11734221</ref> <ref>PMID:12019181</ref> <ref>PMID:11997495</ref> <ref>PMID:15147734</ref> <ref>PMID:15486195</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/d7/3d7v_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=3d7v 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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Like Bcl-2, Mcl-1 is an important survival factor for many cancers, its expression contributing to chemoresistance and disease relapse. However, unlike other prosurvival Bcl-2-like proteins, Mcl-1 stability is acutely regulated. For example, the Bcl-2 homology 3 (BH3)-only protein Noxa, which preferentially binds to Mcl-1, also targets it for proteasomal degradation. In this paper, we describe the discovery and characterization of a novel BH3-like ligand derived from Bim, Bim(S)2A, which is highly selective for Mcl-1. Unlike Noxa, Bim(S)2A is unable to trigger Mcl-1 degradation, yet, like Noxa, Bim(S)2A promotes cell killing only when Bcl-x(L) is absent or neutralized. Furthermore, killing by endogenous Bim is not associated with Mcl-1 degradation. Thus, functional inactivation of Mcl-1 does not always require its elimination. Rather, it can be efficiently antagonized by a BH3-like ligand tightly engaging its binding groove, which is confirmed here with a structural study. Our data have important implications for the discovery of compounds that might kill cells whose survival depends on Mcl-1.
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===Crystal structure of Mcl-1 in complex with an Mcl-1 selective BH3 ligand===
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A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation.,Lee EF, Czabotar PE, van Delft MF, Michalak EM, Boyle MJ, Willis SN, Puthalakath H, Bouillet P, Colman PM, Huang DC, Fairlie WD J Cell Biol. 2008 Jan 28;180(2):341-55. Epub 2008 Jan 21. PMID:18209102<ref>PMID:18209102</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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The line below this paragraph, {{ABSTRACT_PUBMED_18209102}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 3d7v" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 18209102 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18209102}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Homo sapiens]]
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3D7V is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus,_homo_sapiens Mus musculus, homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D7V OCA].
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[[Category: Large Structures]]
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[[Category: Mus musculus]]
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==Reference==
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[[Category: Synthetic construct]]
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A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation., Lee EF, Czabotar PE, van Delft MF, Michalak EM, Boyle MJ, Willis SN, Puthalakath H, Bouillet P, Colman PM, Huang DC, Fairlie WD, J Cell Biol. 2008 Jan 28;180(2):341-55. Epub 2008 Jan 21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18209102 18209102]
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[[Category: Colman PM]]
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[[Category: Mus musculus, homo sapiens]]
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[[Category: Czabotar PE]]
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[[Category: Protein complex]]
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[[Category: Fairlie WD]]
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[[Category: Colman, P M.]]
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[[Category: Lee EF]]
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[[Category: Czabotar, P E.]]
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[[Category: Fairlie, W D.]]
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[[Category: Lee, E F.]]
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[[Category: Alternative splicing]]
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[[Category: Amphipathic helix]]
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[[Category: Apoptosis]]
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[[Category: Cytoplasm]]
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[[Category: Developmental protein]]
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[[Category: Differentiation]]
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[[Category: Helical bundle]]
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[[Category: Membrane]]
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[[Category: Mitochondrion]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Polymorphism]]
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[[Category: Transmembrane]]
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[[Category: Ubl conjugation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:28:05 2008''
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Current revision

Crystal structure of Mcl-1 in complex with an Mcl-1 selective BH3 ligand

PDB ID 3d7v

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