6m07: Difference between revisions
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New page: '''Unreleased structure''' The entry 6m07 is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Crystal structure of Lp-PLA2 in complex with a novel covalent inhibitor== | |||
<StructureSection load='6m07' size='340' side='right'caption='[[6m07]], [[Resolution|resolution]] 2.64Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M07 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]] 2.64Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BWO:(E)-N-[2-(diethylamino)ethyl]-3-[(2S)-1-methanoylpyrrolidin-2-yl]-3-oxidanyl-N-[[4-[4-(trifluoromethyl)-2-[2,2,2-tris(fluoranyl)ethoxy]phenyl]phenyl]methyl]prop-2-enamide'>BWO</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=6m07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m07 OCA], [https://pdbe.org/6m07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m07 RCSB], [https://www.ebi.ac.uk/pdbsum/6m07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m07 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Covalent ligands are of great interest as therapeutic drugs or biochemical tools. Here, we reported the discovery of highly selective and irreversible inhibitors of lipoprotein-associated phospholipase A2 (Lp-PLA2) using a covalent fragment-based approach. The crystal structure of Lp-PLA2 in complex with a covalent fragment not only reveals the covalent reaction mechanism but also provides a good starting point to design compound 8, which has a more than 130,000-fold and 3900-fold increase in potency and selectivity, respectively, compared to those of the covalent fragment. Furthermore, fluorescent probes with high selectivity and sensitivity are developed to characterize Lp-PLA2 and its enzymatic activity in vitro or even in living cells in a way more convenient than immunoblotting tests or immunofluorescence imaging. Overall, we provide a paradigm for application of the covalent fragment-based strategy in covalent ligand discovery and the advantage of enol-cyclocarbamate as a new warhead in designing covalent inhibitors of serine hydrolases. | |||
Identification of Highly Selective Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors by a Covalent Fragment-Based Approach.,Huang F, Hu H, Wang K, Peng C, Xu W, Zhang Y, Gao J, Liu Y, Zhou H, Huang R, Li M, Shen J, Xu Y J Med Chem. 2020 Jul 9;63(13):7052-7065. doi: 10.1021/acs.jmedchem.0c00372. Epub , 2020 Jun 10. PMID:32459096<ref>PMID:32459096</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6m07" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Hu HC]] | |||
[[Category: Xu YC]] | |||
Latest revision as of 11:11, 30 October 2024
Crystal structure of Lp-PLA2 in complex with a novel covalent inhibitor
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