9mb4: Difference between revisions
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==Metal Beta Lactamase NDM-1 in Complex with Dual MBL/SBL Inhibitor 14== | |||
<StructureSection load='9mb4' size='340' side='right'caption='[[9mb4]], [[Resolution|resolution]] 2.44Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9mb4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9MB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MB4 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]] 2.441Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1ENL:3,3-bis(oxidanyl)-9-[(4-thiophen-2-yl-1,2,3-triazol-1-yl)methyl]-2,5-dioxa-3-boranuidabicyclo[4.4.0]deca-1(6),7,9-triene-10-carboxylic+acid'>A1ENL</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=9mb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9mb4 OCA], [https://pdbe.org/9mb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9mb4 RCSB], [https://www.ebi.ac.uk/pdbsum/9mb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9mb4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. | |||
<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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9mb4" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Klebsiella pneumoniae]] | |||
[[Category: Large Structures]] | |||
[[Category: Li G-B]] | |||
[[Category: Wei S-Q]] | |||
[[Category: Yang Z-B]] | |||
Latest revision as of 09:01, 11 March 2026
Metal Beta Lactamase NDM-1 in Complex with Dual MBL/SBL Inhibitor 14
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