1r2d: Difference between revisions

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New page: left|200px<br /> <applet load="1r2d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r2d, resolution 1.95Å" /> '''Structure of Human ...
 
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[[Image:1r2d.gif|left|200px]]<br />
<applet load="1r2d" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1r2d, resolution 1.95&Aring;" />
'''Structure of Human Bcl-XL at 1.95 Angstroms'''<br />


==Overview==
==Structure of Human Bcl-XL at 1.95 Angstroms==
Cells expressing high levels of the BCL-X(L) anti-apoptotic protein are, preferentially killed by the mitochondrial inhibitor antimycin A (AA)., Computational modeling predicts a binding site for AA in the extended, hydrophobic groove on BCL-X(L), previously identified as an interface for, dimerization to BAX and related proapoptotic proteins. Here, we identify, BCL-X(L) hydrophobic groove mutants with normal cellular anti-apoptotic, function but suppressed sensitivity to AA. The LD(50) of AA for cells, expressing BCL-X(L) mutants directly correlates with the measured in vitro, dissociation constants for AA binding. These results indicate that, BCL-X(L) is a principal target mediating AA cytotoxicity.
<StructureSection load='1r2d' size='340' side='right'caption='[[1r2d]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1r2d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R2D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R2D FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1r2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r2d OCA], [https://pdbe.org/1r2d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r2d RCSB], [https://www.ebi.ac.uk/pdbsum/1r2d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r2d ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B2CL1_HUMAN B2CL1_HUMAN] 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:19917720</ref> <ref>PMID:21840391</ref>  Isoform Bcl-X(S) promotes apoptosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</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/r2/1r2d_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=1r2d ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cells expressing high levels of the BCL-X(L) anti-apoptotic protein are preferentially killed by the mitochondrial inhibitor antimycin A (AA). Computational modeling predicts a binding site for AA in the extended hydrophobic groove on BCL-X(L), previously identified as an interface for dimerization to BAX and related proapoptotic proteins. Here, we identify BCL-X(L) hydrophobic groove mutants with normal cellular anti-apoptotic function but suppressed sensitivity to AA. The LD(50) of AA for cells expressing BCL-X(L) mutants directly correlates with the measured in vitro dissociation constants for AA binding. These results indicate that BCL-X(L) is a principal target mediating AA cytotoxicity.


==About this Structure==
Bcl-XL mutations suppress cellular sensitivity to antimycin A.,Manion MK, O'Neill JW, Giedt CD, Kim KM, Zhang KY, Hockenbery DM J Biol Chem. 2004 Jan 16;279(3):2159-65. Epub 2003 Oct 8. PMID:14534311<ref>PMID:14534311</ref>
1R2D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R2D OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Bcl-XL mutations suppress cellular sensitivity to antimycin A., Manion MK, O'Neill JW, Giedt CD, Kim KM, Zhang KY, Hockenbery DM, J Biol Chem. 2004 Jan 16;279(3):2159-65. Epub 2003 Oct 8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14534311 14534311]
</div>
<div class="pdbe-citations 1r2d" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Giedt, C.D.]]
[[Category: Giedt CD]]
[[Category: Hockenbery, D.M.]]
[[Category: Hockenbery DM]]
[[Category: Kim, K.M.]]
[[Category: Kim KM]]
[[Category: Manion, M.K.]]
[[Category: Manion MK]]
[[Category: Neill, J.W.O.]]
[[Category: O'Neill JW]]
[[Category: Zhang, K.Y.]]
[[Category: Zhang KY]]
[[Category: alpha-helical]]
[[Category: apoptosis]]
[[Category: monomeric]]
 
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Retrieved from "https://proteopedia.org/1r2d"