4bpk

From Proteopedia

(Difference between revisions)

Revision as of 12:32, 4 August 2016

Bcl-xL bound to alpha beta Puma BH3 peptide 5

Structural highlights

4bpk is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:	, , , , , , , ,
Related:	4bpi, 4bpj
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]

Publication Abstract from PubMed

We have used computational methods to improve the affinity of a foldamer ligand for its target protein. The effort began with a previously reported alpha/beta-peptide based on the BH3 domain of the proapoptotic protein Puma; this foldamer binds tightly to Bcl-x(L) but weakly to Mcl-1. The crystal structure of the Puma-derived alpha/beta-peptide complexed to Bcl-x(L) was used as the basis for computational design of variants intended to display improved binding to Mcl-1. Molecular modelling suggested modification of three alpha residues of the original alpha/beta backbone. Individually, each substitution caused only a modest (4- to 15-fold) gain in affinity; however, together the three substitutions led to a 250-fold increase in binding to Mcl-1. These modifications had very little effect on affinity for Bcl-x(L). Crystal structures of a number of the new alpha/beta-peptides bound to either Mcl-1 or Bcl-x(L) validated the selection of each substitution. Overall, our findings demonstrate that structure-guided rational design can be used to improve affinity and alter partner selectivity of peptidic ligands with unnatural backbones that bind to specific protein partners.

Structure-guided rational design of alpha/beta-peptide foldamers with high affinity for BCL-2 family prosurvival proteins.,Smith BJ, Lee EF, Checco JW, Evangelista M, Gellman SH, Fairlie WD Chembiochem. 2013 Sep 2;14(13):1564-72. doi: 10.1002/cbic.201300351. Epub 2013, Aug 8. PMID:23929624^[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
↑ Smith BJ, Lee EF, Checco JW, Evangelista M, Gellman SH, Fairlie WD. Structure-guided rational design of alpha/beta-peptide foldamers with high affinity for BCL-2 family prosurvival proteins. Chembiochem. 2013 Sep 2;14(13):1564-72. doi: 10.1002/cbic.201300351. Epub 2013, Aug 8. PMID:23929624 doi:http://dx.doi.org/10.1002/cbic.201300351

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/4bpk"

@@ Line 1: / Line 1: @@
 ==Bcl-xL bound to alpha beta Puma BH3 peptide 5==
 <StructureSection load='4bpk' size='340' side='right' caption='[[4bpk]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <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=AHP:2-AMINO-HEPTANOIC+ACID'>AHP</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 id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bpi|4bpi]], [[4bpj|4bpj]]</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=4bpk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bpk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bpk RCSB], [http://www.ebi.ac.uk/pdbsum/4bpk PDBsum]</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=4bpk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bpk OCA], [http://pdbe.org/4bpk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bpk RCSB], [http://www.ebi.ac.uk/pdbsum/4bpk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bpk ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4bpk" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4bpk

From Proteopedia

Revision as of 12:32, 4 August 2016

Bcl-xL bound to alpha beta Puma BH3 peptide 5

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox