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3d7v

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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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<StructureSection load='3d7v' size='340' side='right' caption='[[3d7v]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3d7v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3D7V FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2nl9|2nl9]], [[2nla|2nla]], [[1wsx|1wsx]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3d7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d7v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3d7v RCSB], [http://www.ebi.ac.uk/pdbsum/3d7v PDBsum]</span></td></tr>
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<table>
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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/chain_selection.php?pdb_ID=2ata 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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{{STRUCTURE_3d7v| PDB=3d7v | SCENE= }}
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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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===Crystal structure of Mcl-1 in complex with an Mcl-1 selective BH3 ligand===
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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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{{ABSTRACT_PUBMED_18209102}}
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==About this Structure==
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[[3d7v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D7V OCA].
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==See Also==
==See Also==
*[[Bcl-2|Bcl-2]]
*[[Bcl-2|Bcl-2]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018209102</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Colman, P M.]]
[[Category: Colman, P M.]]

Revision as of 09:57, 29 September 2014

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

3d7v, resolution 2.03Å

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