1r2d: Difference between revisions

Latest revision as of 05:59, 23 August 2023

Structure of Human Bcl-XL at 1.95 Angstroms

Structural highlights

1r2d is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.95Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] Isoform Bcl-X(S) promotes apoptosis.^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
↑ Manion MK, O'Neill JW, Giedt CD, Kim KM, Zhang KY, Hockenbery DM. Bcl-XL mutations suppress cellular sensitivity to antimycin A. J Biol Chem. 2004 Jan 16;279(3):2159-65. Epub 2003 Oct 8. PMID:14534311 doi:https://dx.doi.org/10.1074/jbc.M306021200

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09

[2] Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017

[3] Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09

[4] Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017

[5] Manion MK, O'Neill JW, Giedt CD, Kim KM, Zhang KY, Hockenbery DM. Bcl-XL mutations suppress cellular sensitivity to antimycin A. J Biol Chem. 2004 Jan 16;279(3):2159-65. Epub 2003 Oct 8. PMID:14534311 doi:https://dx.doi.org/10.1074/jbc.M306021200

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[2]

[3]

[4]

[5]

@@ Line 3: / Line 3: @@
 <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 [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=1R2D FirstGlance]. <br>
+<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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1maz|1maz]], [[1r2e|1r2e]], [[1r2g|1r2g]], [[1r2h|1r2h]], [[1r2i|1r2i]]</div></td></tr>
+</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCL-XL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1r2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r2d OCA], [http://pdbe.org/1r2d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1r2d RCSB], [http://www.ebi.ac.uk/pdbsum/1r2d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1r2d ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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]]
@@ Line 36: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[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]]

1r2d: Difference between revisions

Latest revision as of 05:59, 23 August 2023

Structure of Human Bcl-XL at 1.95 Angstroms

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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