2yj1

From Proteopedia

(Difference between revisions)

Revision as of 08:10, 25 December 2014

PUMA BH3 FOLDAMER IN COMPLEX WITH BCL-XL

Structural highlights

2yj1 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	, , , , , , ,
Related:	1bxl, 1ysi, 2b48, 1r2e, 1ysg, 1ysn, 1r2g, 1r2h, 1lxl, 1r2d, 1g5j, 1maz, 1r2i
Resources:	FirstGlance, OCA, RCSB, PDBsum

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]

Publication Abstract from PubMed

The crystal structure of a complex between the prosurvival protein Bcl-x(L) and an alpha/beta-peptide 21-mer is described. The alpha/beta-peptide contains six beta-amino acid residues distributed periodically throughout the sequence and adopts an alpha-helix-like conformation that mimics the bioactive shape of the Puma BH3 domain. The alpha/beta-peptide forms all of the noncovalent contacts that have previously been identified as necessary for recognition of the prosurvival protein by an authentic BH3 domain. Comparison of our alpha/beta-peptide:Bcl-x(L) structure with structures of complexes between native BH3 domains and Bcl-2 family proteins reveals how subtle adjustments, including variations in helix radius and helix bowing, allow the alpha/beta-peptide to engage Bcl-x(L) with high affinity. Geometric comparisons of the BH3-mimetic alpha/beta-peptide with alpha/beta-peptides in helix-bundle assemblies provide insight on the conformational plasticity of backbones that contain combinations of alpha- and beta-amino acid residues. The BH3-mimetic alpha/beta-peptide displays prosurvival protein-binding preferences distinct from those of Puma BH3 itself, even though these two oligomers have identical side-chain sequences. Our results suggest origins for this backbone-dependent change in selectivity.

Structural Basis of Bcl-x(L) Recognition by a BH3-Mimetic alpha/beta-Peptide Generated by Sequence-Based Design.,Lee EF, Smith BJ, Horne WS, Mayer KN, Evangelista M, Colman PM, Gellman SH, Fairlie WD Chembiochem. 2011 Sep 5;12(13):2025-32. doi: 10.1002/cbic.201100314. Epub, 2011 Jul 8. PMID:21744457^[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
↑ Lee EF, Smith BJ, Horne WS, Mayer KN, Evangelista M, Colman PM, Gellman SH, Fairlie WD. Structural Basis of Bcl-x(L) Recognition by a BH3-Mimetic alpha/beta-Peptide Generated by Sequence-Based Design. Chembiochem. 2011 Sep 5;12(13):2025-32. doi: 10.1002/cbic.201100314. Epub, 2011 Jul 8. PMID:21744457 doi:10.1002/cbic.201100314

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2yj1"

@@ Line 2: / Line 2: @@
 <StructureSection load='2yj1' size='340' side='right' caption='[[2yj1]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2yj1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YJ1 OCA]. <br>
+<table><tr><td colspan='2'>[[2yj1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YJ1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YJ1 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=B3A:(3S)-3-AMINOBUTANOIC+ACID'>B3A</scene>, <scene name='pdbligand=B3D:3-AMINOPENTANEDIOIC+ACID'>B3D</scene>, <scene name='pdbligand=B3E:(3S)-3-AMINOHEXANEDIOIC+ACID'>B3E</scene>, <scene name='pdbligand=B3Q:(3S)-3,6-DIAMINO-6-OXOHEXANOIC+ACID'>B3Q</scene>, <scene name='pdbligand=HR7:(3S)-3-AMINO-6-[(DIAMINOMETHYLIDENE)AMINO]HEXANOIC+ACID'>HR7</scene>, <scene name='pdbligand=HT7:(3S)-3-AMINO-4-(1H-INDOL-3-YL)BUTANOIC+ACID'>HT7</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=B3A:(3S)-3-AMINOBUTANOIC+ACID'>B3A</scene>, <scene name='pdbligand=B3D:3-AMINOPENTANEDIOIC+ACID'>B3D</scene>, <scene name='pdbligand=B3E:(3S)-3-AMINOHEXANEDIOIC+ACID'>B3E</scene>, <scene name='pdbligand=B3Q:(3S)-3,6-DIAMINO-6-OXOHEXANOIC+ACID'>B3Q</scene>, <scene name='pdbligand=HR7:(3S)-3-AMINO-6-[(DIAMINOMETHYLIDENE)AMINO]HEXANOIC+ACID'>HR7</scene>, <scene name='pdbligand=HT7:(3S)-3-AMINO-4-(1H-INDOL-3-YL)BUTANOIC+ACID'>HT7</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bxl|1bxl]], [[1ysi|1ysi]], [[2b48|2b48]], [[1r2e|1r2e]], [[1ysg|1ysg]], [[1ysn|1ysn]], [[1r2g|1r2g]], [[1r2h|1r2h]], [[1lxl|1lxl]], [[1r2d|1r2d]], [[1g5j|1g5j]], [[1maz|1maz]], [[1r2i|1r2i]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bxl|1bxl]], [[1ysi|1ysi]], [[2b48|2b48]], [[1r2e|1r2e]], [[1ysg|1ysg]], [[1ysn|1ysn]], [[1r2g|1r2g]], [[1r2h|1r2h]], [[1lxl|1lxl]], [[1r2d|1r2d]], [[1g5j|1g5j]], [[1maz|1maz]], [[1r2i|1r2i]]</td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></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=2yj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yj1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yj1 RCSB], [http://www.ebi.ac.uk/pdbsum/2yj1 PDBsum]</span></td></tr>
-<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=2yj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yj1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yj1 RCSB], [http://www.ebi.ac.uk/pdbsum/2yj1 PDBsum]</span></td></tr>
+</table>
-<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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 14: / Line 15: @@
 Structural Basis of Bcl-x(L) Recognition by a BH3-Mimetic alpha/beta-Peptide Generated by Sequence-Based Design.,Lee EF, Smith BJ, Horne WS, Mayer KN, Evangelista M, Colman PM, Gellman SH, Fairlie WD Chembiochem. 2011 Sep 5;12(13):2025-32. doi: 10.1002/cbic.201100314. Epub, 2011 Jul 8. PMID:21744457<ref>PMID:21744457</ref>
-From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
 == References ==
@@ Line 21: / Line 22: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Colman, P M.]]
+[[Category: Colman, P M]]
-[[Category: Evangelista, M.]]
+[[Category: Evangelista, M]]
-[[Category: Fairlie, W D.]]
+[[Category: Fairlie, W D]]
-[[Category: Gellman, S H.]]
+[[Category: Gellman, S H]]
-[[Category: Horne, W S.]]
+[[Category: Horne, W S]]
-[[Category: Lee, E F.]]
+[[Category: Lee, E F]]
-[[Category: Mayer, K N.]]
+[[Category: Mayer, K N]]
-[[Category: Smith, B J.]]
+[[Category: Smith, B J]]
 [[Category: Apoptosis]]
 [[Category: Autophagy]]

2yj1

From Proteopedia

Revision as of 08:10, 25 December 2014

PUMA BH3 FOLDAMER IN COMPLEX WITH BCL-XL

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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