8rpo
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==BFL1 in complex with a reversible covalent ligand== | |
| + | <StructureSection load='8rpo' size='340' side='right'caption='[[8rpo]], [[Resolution|resolution]] 1.79Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8rpo]] is a 1 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=8RPO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8RPO 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]] 1.791Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1H2C:(~{E})-2-cyano-3-(2-dimethylphosphorylphenyl)-~{N}-[[1-[4-(trifluoromethyl)phenyl]cyclopropyl]methyl]prop-2-enamide'>A1H2C</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=8rpo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8rpo OCA], [https://pdbe.org/8rpo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8rpo RCSB], [https://www.ebi.ac.uk/pdbsum/8rpo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8rpo 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 == | ||
| + | Bfl-1 is overexpressed in both hematological and solid tumors; therefore, inhibitors of Bfl-1 are highly desirable. A DNA-encoded chemical library (DEL) screen against Bfl-1 identified the first known reversible covalent small-molecule ligand for Bfl-1. The binding was validated through biophysical and biochemical techniques, which confirmed the reversible covalent mechanism of action and pointed to binding through Cys55. This represented the first identification of a cyano-acrylamide reversible covalent compound from a DEL screen and highlights further opportunities for covalent drug discovery through DEL screening. A 10-fold improvement in potency was achieved through a systematic SAR exploration of the hit. The more potent analogue compound 13 was successfully cocrystallized in Bfl-1, revealing the binding mode and providing further evidence of a covalent interaction with Cys55. | ||
| - | + | Identification and Evaluation of Reversible Covalent Binders to Cys55 of Bfl-1 from a DNA-Encoded Chemical Library Screen.,Lucas SCC, Blackwell JH, Borjesson U, Hargreaves D, Milbradt AG, Ahmed S, Bostock MJ, Guerot C, Gohlke A, Kinzel O, Lamb ML, Selmi N, Stubbs CJ, Su N, Su Q, Luo H, Xiong T, Zuo X, Bazzaz S, Bienstock C, Centrella PA, Denton KE, Gikunju D, Guie MA, Guilinger JP, Hupp C, Keefe AD, Satoh T, Zhang Y, Rivers EL ACS Med Chem Lett. 2024 May 20;15(6):791-797. doi: , 10.1021/acsmedchemlett.4c00113. eCollection 2024 Jun 13. PMID:38894895<ref>PMID:38894895</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Hargreaves | + | <div class="pdbe-citations 8rpo" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hargreaves D]] | ||
Current revision
BFL1 in complex with a reversible covalent ligand
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