7yha: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7yha is ON HOLD  until Paper Publication
+==Crystal structure of IMP-1 MBL in complex with (3-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzyl)phosphonic acid==
+<StructureSection load='7yha' size='340' side='right'caption='[[7yha]], [[Resolution|resolution]] 2.13&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7yha]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YHA 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]] 2.135&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ITK:[3-[4-(4-methylphenyl)-1,2,3-triazol-1-yl]phenyl]methylphosphonic+acid'>ITK</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7yha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yha OCA], [https://pdbe.org/7yha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yha RCSB], [https://www.ebi.ac.uk/pdbsum/7yha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yha ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q79MP6_PSEAI Q79MP6_PSEAI]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The emergence of metallo-beta-lactamases (MBLs) confers resistance to nearly all the beta-lactam antibiotics, including carbapenems. Currently, there is a lack of clinically useful MBL inhibitors, making it crucial to discover new inhibitor chemotypes that can potently target multiple clinically relevant MBLs. Herein we report a strategy that utilizes a metal binding pharmacophore (MBP) click approach to identify new broad-spectrum MBL inhibitors. Our initial investigation identified several MBPs including phthalic acid, phenylboronic acid and benzyl phosphoric acid, which were subjected to structural transformations using azide-alkyne click reactions. Subsequent structure-activity relationship analyses led to the identification of several potent broad-spectrum MBL inhibitors, including 73 that manifested IC(50) values ranging from 0.00012 muM to 0.64 muM against multiple MBLs. Co-crystallographic studies demonstrated the importance of MBPs in engaging with the MBL active site anchor pharmacophore features, and revealed the unusual two-molecule binding modes with IMP-1, highlighting the critical role of flexible active site loops in recognizing structurally diverse substrates/inhibitors. Our work provides new chemotypes for MBL inhibition and establishes a MBP click-derived paradigm for inhibitor discovery targeting MBLs as well as other metalloenzymes.
-Authors: Li, G.-B., Yan, Y.-H.
+Metal binding pharmacophore click-derived discovery of new broad-spectrum metallo-beta-lactamase inhibitors.,Yan YH, Ding HS, Zhu KR, Mu BS, Zheng Y, Huang MY, Zhou C, Li WF, Wang Z, Wu Y, Li GB Eur J Med Chem. 2023 May 13;257:115473. doi: 10.1016/j.ejmech.2023.115473. PMID:37209449<ref>PMID:37209449</ref>
-Description: Crystal structure of IMP-1 MBL in complex with (3-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzyl)phosphonic acid
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Yan, Y.-H]]
+<div class="pdbe-citations 7yha" style="background-color:#fffaf0;"></div>
-[[Category: Li, G.-B]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Pseudomonas aeruginosa]]
+[[Category: Li G-B]]
+[[Category: Yan Y-H]]