4g35: Difference between revisions
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New page: '''Unreleased structure''' The entry 4g35 is ON HOLD Authors: Drake, Eric , Edwardraja, Selvakumar , Lin, Qing , Gulick, Andrew M. Description: Mcl-1 in complex with a biphenyl cross-l... |
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==Mcl-1 in complex with a biphenyl cross-linked Noxa peptide.== | |||
<StructureSection load='4g35' size='340' side='right'caption='[[4g35]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4g35]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G35 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G35 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]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4BP:4,4-BIS(BROMOMETHYL)BIPHENYL'>4BP</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DCY:D-CYSTEINE'>DCY</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=4g35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g35 OCA], [https://pdbe.org/4g35 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g35 RCSB], [https://www.ebi.ac.uk/pdbsum/4g35 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g35 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MCL1_MOUSE MCL1_MOUSE] Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Direct chemical modifications provide a simple and effective means to "translate" bioactive helical peptides into potential therapeutics targeting intracellular protein-protein interactions. We previously showed that distance-matching bisaryl cross-linkers can reinforce peptide helices containing two cysteines at the i and i+7 positions and confer cell permeability to the cross-linked peptides. Here we report the first crystal structure of a biphenyl-cross-linked Noxa peptide in complex with its target Mcl-1 at 2.0 A resolution. Guided by this structure, we remodeled the surface of this cross-linked peptide through side-chain substitution and N-methylation and obtained a pair of cross-linked peptides with substantially increased helicity, cell permeability, proteolytic stability, and cell-killing activity in Mcl-1-overexpressing U937 cells. | |||
Rational design of proteolytically stable, cell-permeable peptide-based selective Mcl-1 inhibitors.,Muppidi A, Doi K, Edwardraja S, Drake EJ, Gulick AM, Wang HG, Lin Q J Am Chem Soc. 2012 Sep 12;134(36):14734-7. doi: 10.1021/ja306864v. Epub 2012 Sep, 4. PMID:22920569<ref>PMID:22920569</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4g35" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Drake E]] | |||
[[Category: Edwardraja S]] | |||
[[Category: Gulick AM]] | |||
[[Category: Lin Q]] | |||
