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5c3f

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Crystal structure of Mcl-1 bound to BID-MM

Structural highlights

5c3f is a 2 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 1.43Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

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^[2]

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

References

↑ Bingle CD, Craig RW, Swales BM, Singleton V, Zhou P, Whyte MK. Exon skipping in Mcl-1 results in a bcl-2 homology domain 3 only gene product that promotes cell death. J Biol Chem. 2000 Jul 21;275(29):22136-46. PMID:10766760 doi:10.1074/jbc.M909572199
↑ Miles JA, Yeo DJ, Rowell P, Rodriguez-Marin S, Pask CM, Warriner SL, Edwards TA, Wilson AJ. Hydrocarbon constrained peptides - understanding preorganisation and binding affinity. Chem Sci. 2016 Jun 1;7(6):3694-3702. doi: 10.1039/c5sc04048e. Epub 2016 Feb 29. PMID:28970875 doi:http://dx.doi.org/10.1039/c5sc04048e

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5c3f"

@@ Line 3: / Line 3: @@
 <StructureSection load='5c3f' size='340' side='right'caption='[[5c3f]], [[Resolution|resolution]] 1.43&Aring;' scene=''>
 == 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C3F FirstGlance]. <br>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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]] 1.43&#8491;</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=NLE:NORLEUCINE'>NLE</scene></td></tr>
+<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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5c3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c3f OCA], [http://pdbe.org/5c3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c3f RCSB], [http://www.ebi.ac.uk/pdbsum/5c3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5c3f ProSAT]</span></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=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>
 == Function ==
-[[http://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>
+[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 ==
@@ Line 26: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Edwards, T A]]
+[[Category: Edwards TA]]
-[[Category: Miles, J A]]
+[[Category: Miles JA]]
-[[Category: Pask, C M]]
+[[Category: Pask CM]]
-[[Category: Rodriguez-Marin, S]]
+[[Category: Rodriguez-Marin S]]
-[[Category: Rowell, P]]
+[[Category: Rowell P]]
-[[Category: Warriner, S L]]
+[[Category: Warriner SL]]
-[[Category: Wilson, A J]]
+[[Category: Wilson AJ]]
-[[Category: Yeo, D J]]
+[[Category: Yeo DJ]]
-[[Category: Apoptosis]]
-[[Category: Bcl-2 family]]
-[[Category: Bh3]]
-[[Category: Complex]]
-[[Category: Stapled peptide]]

5c3f

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Current revision

Crystal structure of Mcl-1 bound to BID-MM

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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