6vbx: Difference between revisions
New page: '''Unreleased structure''' The entry 6vbx is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Crystal structure of Mcl-1 in complex with 138E12 peptide, Lys-covalent antagonist== | |||
<StructureSection load='6vbx' size='340' side='right'caption='[[6vbx]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6vbx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VBX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VBX 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]] 1.95Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QX7:N-acetyl-3-{[5-(fluorosulfonyl)-2-methylbenzene-1-carbonyl]amino}-L-alanine'>QX7</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=6vbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vbx OCA], [https://pdbe.org/6vbx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vbx RCSB], [https://www.ebi.ac.uk/pdbsum/6vbx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vbx ProSAT]</span></td></tr> | |||
</table> | |||
== 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 == | |||
Modulating disease-relevant protein-protein interactions (PPIs) using pharmacological tools is a critical step toward the design of novel therapeutic strategies. Over the years, however, targeting PPIs has proven a very challenging task owing to the large interfacial areas. Our recent efforts identified possible novel routes for the design of potent and selective inhibitors of PPIs using a structure-based design of covalent inhibitors targeting Lys residues. In this present study, we report on the design, synthesis, and characterizations of the first Lys-covalent BH3 peptide that has a remarkable affinity and selectivity for hMcl-1 over the closely related hBfl-1 protein. Our structural studies, aided by X-ray crystallography, provide atomic-level details of the inhibitor interactions that can be used to further translate these discoveries into novel generation, Lys-covalent pro-apoptotic agents. | |||
Design, Synthesis, and Structural Characterization of Lysine Covalent BH3 Peptides Targeting Mcl-1.,Gambini L, Udompholkul P, Baggio C, Muralidharan A, Kenjic N, Assar Z, Perry JJP, Pellecchia M J Med Chem. 2021 Apr 22;64(8):4903-4912. doi: 10.1021/acs.jmedchem.1c00005. Epub , 2021 Apr 2. PMID:33797903<ref>PMID:33797903</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6vbx" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Assar Z]] | |||
[[Category: Kenjic N]] | |||
[[Category: Pellecchia M]] | |||
[[Category: Perry JJ]] | |||
Latest revision as of 11:08, 11 October 2023
Crystal structure of Mcl-1 in complex with 138E12 peptide, Lys-covalent antagonistCrystal structure of Mcl-1 in complex with 138E12 peptide, Lys-covalent antagonist
Structural highlights
FunctionMCL1_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 PubMedModulating disease-relevant protein-protein interactions (PPIs) using pharmacological tools is a critical step toward the design of novel therapeutic strategies. Over the years, however, targeting PPIs has proven a very challenging task owing to the large interfacial areas. Our recent efforts identified possible novel routes for the design of potent and selective inhibitors of PPIs using a structure-based design of covalent inhibitors targeting Lys residues. In this present study, we report on the design, synthesis, and characterizations of the first Lys-covalent BH3 peptide that has a remarkable affinity and selectivity for hMcl-1 over the closely related hBfl-1 protein. Our structural studies, aided by X-ray crystallography, provide atomic-level details of the inhibitor interactions that can be used to further translate these discoveries into novel generation, Lys-covalent pro-apoptotic agents. Design, Synthesis, and Structural Characterization of Lysine Covalent BH3 Peptides Targeting Mcl-1.,Gambini L, Udompholkul P, Baggio C, Muralidharan A, Kenjic N, Assar Z, Perry JJP, Pellecchia M J Med Chem. 2021 Apr 22;64(8):4903-4912. doi: 10.1021/acs.jmedchem.1c00005. Epub , 2021 Apr 2. PMID:33797903[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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