5c3f: Difference between revisions
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==Crystal structure of Mcl-1 bound to BID-MM== | ==Crystal structure of Mcl-1 bound to BID-MM== | ||
<StructureSection load='5c3f' size='340' side='right' caption='[[5c3f]], [[Resolution|resolution]] 1.43Å' scene=''> | <StructureSection load='5c3f' size='340' side='right'caption='[[5c3f]], [[Resolution|resolution]] 1.43Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5c3f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C3F OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5c3f]] is a 2 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=5C3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C3F FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.43Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5c3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c3f OCA], [https://pdbe.org/5c3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c3f RCSB], [https://www.ebi.ac.uk/pdbsum/5c3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c3f ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/MCL1_HUMAN MCL1_HUMAN] 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. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.<ref>PMID:10766760</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The development of constrained peptides represents an emerging strategy to generate peptide based probes and hits for drug-discovery that address challenging protein-protein interactions (PPIs). In this manuscript we report on the use of a novel alpha-alkenylglycine derived amino acid to synthesise hydrocarbon constrained BH3-family sequences (BIM and BID). Our biophysical and structural analyses illustrate that whilst the introduction of the constraint increases the population of the bioactive alpha-helical conformation of the peptide in solution, it does not enhance the inhibitory potency against pro-apoptotic Bcl-xL and Mcl-1 PPIs. SPR analyses indicate binding occurs via an induced fit mechanism whilst X-ray analyses illustrate none of the key interactions between the helix and protein are disturbed. The behaviour derives from enthalpy-entropy compensation which may be considered in terms of the ground state energies of the unbound constrained and unconstrained peptides; this has implications for the design of preorganised peptides to target protein-protein interactions. | |||
Hydrocarbon constrained peptides - understanding preorganisation and binding affinity.,Miles JA, Yeo DJ, Rowell P, Rodriguez-Marin S, Pask CM, Warriner SL, Edwards TA, Wilson AJ Chem Sci. 2016 Jun 1;7(6):3694-3702. doi: 10.1039/c5sc04048e. Epub 2016 Feb 29. PMID:28970875<ref>PMID:28970875</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5c3f" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Edwards TA]] | ||
[[Category: | [[Category: Miles JA]] | ||
[[Category: | [[Category: Pask CM]] | ||
[[Category: | [[Category: Rodriguez-Marin S]] | ||
[[Category: | [[Category: Rowell P]] | ||
[[Category: | [[Category: Warriner SL]] | ||
[[Category: | [[Category: Wilson AJ]] | ||
[[Category: | [[Category: Yeo DJ]] | ||
Latest revision as of 11:18, 10 January 2024
Crystal structure of Mcl-1 bound to BID-MM
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