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{{STRUCTURE_3ilb|  PDB=3ilb  |  SCENE=  }}
==Crystal structure of mouse Bcl-xl mutant (R139A) at pH 6.0==
===Crystal structure of mouse Bcl-xl mutant (R139A) at pH 6.0===
<StructureSection load='3ilb' size='340' side='right' caption='[[3ilb]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
{{ABSTRACT_PUBMED_20206602}}
== Structural highlights ==
<table><tr><td colspan='2'>[[3ilb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ILB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ILB FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ihc|3ihc]], [[3iih|3iih]], [[3ihd|3ihd]], [[3ihe|3ihe]], [[3iig|3iig]], [[3ihf|3ihf]], [[3ilc|3ilc]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Bcl-xl, Bcl2l, Bcl2l1, Bclx ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ilb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ilb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ilb RCSB], [http://www.ebi.ac.uk/pdbsum/3ilb PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/B2CL1_MOUSE B2CL1_MOUSE]] 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:9390687</ref>  Isoform Bcl-X(S) promotes apoptosis (By similarity).<ref>PMID:9390687</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/il/3ilb_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
This study reports the crystal structures of Bcl-xl wild type and three Bcl-xl mutants (Y101A, F105A, and R139A) with amino acid substitutions in the hydrophobic groove of the Bcl-xl BH3 domain. An additional 12 ordered residues were observed in a highly flexible loop between the alpha1 and alpha2 helices, and were recognized as an important deamidation site for the regulation of apoptosis. The autophagy-effector protein, Beclin 1, contains a novel BH3 domain (residues 101-125), which binds to the surface cleft of Bcl-xl, as confirmed by nuclear magnetic resonance (NMR) spectroscopy and analytical gel-filtration results. Gossypol, a potent inhibitor of Bcl-xl, had a K(d) value of 0.9 microM. In addition, the structural and biochemical analysis of five Bcl-xl substitution mutants will provide structural insights into the design and development of anti-cancer drugs.


==Function==
Structural insights into mouse anti-apoptotic Bcl-xl reveal affinity for Beclin 1 and gossypol.,Priyadarshi A, Roy A, Kim KS, Kim EE, Hwang KY Biochem Biophys Res Commun. 2010 Apr 9;394(3):515-21. Epub 2010 Mar 4. PMID:20206602<ref>PMID:20206602</ref>
[[http://www.uniprot.org/uniprot/B2CL1_MOUSE B2CL1_MOUSE]] 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:9390687</ref>  Isoform Bcl-X(S) promotes apoptosis (By similarity).<ref>PMID:9390687</ref>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[3ilb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ILB OCA].
</div>


==See Also==
==See Also==
*[[Bcl-2|Bcl-2]]
*[[Bcl-2|Bcl-2]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:020206602</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Lk3 transgenic mice]]
[[Category: Hwang, K Y.]]
[[Category: Hwang, K Y]]
[[Category: Priyadarshi, A.]]
[[Category: Priyadarshi, A]]
[[Category: Apoptosis]]
[[Category: Apoptosis]]
[[Category: Bcl-2]]
[[Category: Bcl-2]]