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9s6m
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of BFL1 in complex with a covalent inhibitor, alternative series, cmpd25== | |
| + | <StructureSection load='9s6m' size='340' side='right'caption='[[9s6m]], [[Resolution|resolution]] 1.43Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9s6m]] 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=9S6M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9S6M 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]] 1.427Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JL2:(1~{R},2~{R})-2-azanyl-~{N}-[4-[(1~{R})-1-[propanoyl-[4-(trifluoromethyloxy)phenyl]amino]ethyl]phenyl]cyclopentane-1-carboxamide'>A1JL2</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=9s6m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9s6m OCA], [https://pdbe.org/9s6m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9s6m RCSB], [https://www.ebi.ac.uk/pdbsum/9s6m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9s6m ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/B2LA1_HUMAN B2LA1_HUMAN] Retards apoptosis induced by IL-3 deprivation. May function in the response of hemopoietic cells to external signals and in maintaining endothelial survival during infection (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We describe herein the discovery and optimization of a potent and irreversible cellular probe for selective labeling of Bfl-1, a member of the Bcl-2 family. This chemical series demonstrates robust selectivity for Bfl-1 over other related antiapoptotic proteins and exhibits favorable cellular potency as well as promising in vivo pharmacokinetics. Notably, compound 25 achieves a k(inact)/K(I) value of 9300 M(-1)s(-1) and elicits caspase activation at submicromolar concentrations in cellular assays. To comprehensively profile proteome-wide selectivity, we performed chemoproteomic analyses on compound 25 alongside our previously reported Bfl-1 inhibitors. This enabled critical insights into potential off-target interactions and facilitated direct comparison of off-target profiles among distinct chemotypes targeting Bfl-1. | ||
| - | + | Optimization and Chemoproteomic Profiling of a Selective, Covalent Bfl-1-Targeting Cellular Tool.,Blackwell JH, Lucas SCC, Battocchio G, Borjesson U, Bostock MJ, Braybrooke EL, Cheung T, Cottee MA, Beaumont KC, Gohlke A, Hargreaves D, van Hoek-Emmelot M, van Hoeven V, Jansen C, Kawatkar A, Kinzel O, Kumar P, Kupcova L, Lainchbury MD, Leon L, Milbradt AG, Palisse A, Schade M, van Rijbroek K, Sacchetto C, Schellekens R, Su N, Xu H, Zhao H, Chen Y, Huang S J Med Chem. 2025 Dec 23. doi: 10.1021/acs.jmedchem.5c02581. PMID:41432228<ref>PMID:41432228</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9s6m" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cottee MA]] | ||
| + | [[Category: Hargreaves D]] | ||
Current revision
Structure of BFL1 in complex with a covalent inhibitor, alternative series, cmpd25
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