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'''Unreleased structure'''


The entry 9mas is ON HOLD  until Paper Publication
==Metal Beta Lactamase VIM-2 in Complex with Dual MBL/SBL Inhibitor 3==
<StructureSection load='9mas' size='340' side='right'caption='[[9mas]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9mas]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9MAS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MAS 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]] 1.757&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1ENM:9-[(4-methylpyrazol-1-yl)methyl]-3,3-bis(oxidanyl)-2,5-dioxa-3-boranuidabicyclo[4.4.0]deca-1(6),7,9-triene-10-carboxylic+acid'>A1ENM</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=9mas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9mas OCA], [https://pdbe.org/9mas PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9mas RCSB], [https://www.ebi.ac.uk/pdbsum/9mas PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9mas ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLBV2_ECOLX BLBV2_ECOLX] Class B beta-lactamase which confers resistance to the beta-lactam antibiotics, including penicillins, cephalosporins and carbapenems (PubMed:20498317, PubMed:31744917). Acts via hydrolysis of the beta-lactam ring (PubMed:20498317, PubMed:24965651). Has penicillin-, cephalosporin- and carbapenem-hydrolyzing activities (PubMed:20498317, PubMed:24965651).<ref>PMID:20498317</ref> <ref>PMID:24965651</ref> <ref>PMID:31744917</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Gram-negative bacterial resistance to beta-lactam antibiotics is a growing clinical problem, largely driven by the production of metallo-beta-lactamases (MBLs) and serine-beta-lactamases (SBLs). Developing dual inhibitors targeting both MBLs and SBLs has emerged as a focus in the fight against beta-lactam resistance. We previously identified the bicyclic oxo-boronate CB1 as a dual MBL/SBL inhibitor through molecular generation based on the binding mode of carbapenem tetrahedral intermediates. Herein, we report the structural optimization of CB1, yielding new bicyclic oxo-boronates with potent dual MBL/SBL inhibition, some of which could potentiate Meropenem efficacy against carbapenem-resistant Gram-negative superbugs. X-ray crystallography revealed a common binding mode of bicyclic oxo-boronates with VIM-2/NDM-1 MBL and OXA-48 SBL, mimicking the binding of carbapenem intermediates. YL6113 exhibited pharmacokinetic characteristics similar to Meropenem and manifested efficacy when combined with Meropenem in a murine sepsis model. This work provides the basis for developing oxo-boronate-based inhibitors targeting MBLs/SBLs and other relevant targets.


Authors: Li, G.-B., Yang, Z.-B., Wei, S.-Q.
Structural Optimization of Bicyclic Oxo-Boronates as Dual Metallo- and Serine-beta-Lactamase Inhibitors.,Yang ZB, Wei SQ, Wang YG, Dong XM, Xu HX, Li XL, Peng J, Yin RC, Li GB J Med Chem. 2025 Oct 23;68(20):21807-21828. doi: 10.1021/acs.jmedchem.5c02230. , Epub 2025 Oct 13. PMID:41082617<ref>PMID:41082617</ref>


Description: Metal Beta Lactamase VIM-2 in Complex with Dual MBL/SBL Inhibitor 3
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Yang, Z.-B]]
<div class="pdbe-citations 9mas" style="background-color:#fffaf0;"></div>
[[Category: Wei, S.-Q]]
== References ==
[[Category: Li, G.-B]]
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Li G-B]]
[[Category: Wei S-Q]]
[[Category: Yang Z-B]]
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