ArticleAntimicrobial agents and chemotherapy2011
Novel insights into the mode of inhibition of class A SHV-1 beta-lactamases revealed by boronic acid transition state inhibitors.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Synergistic Potential of Repurposing non-β-lactam Compounds as Class A serine β-lactamases Inhibitor: Insights from MolecularDocking, Molecular Dynamics Simulations and Antimicrobial Potentiation.Scientific reports · 2026Article
- Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Discovery of Boronic Acids-Based β-Lactamase Inhibitors Through In Situ Click Chemistry.International journal of molecular sciences · 2025Article
- Activity of Organoboron Compounds against Biofilm-Forming Pathogens.Antibiotics (Basel, Switzerland) · 2024Review
- X-ray Crystallography Deciphers the Activity of Broad-Spectrum Boronic Acid β-Lactamase Inhibitors.ACS medicinal chemistry letters · 2019Article
- Computational analysis of the interactions of a novel cephalosporin derivative with β-lactamases.BMC structural biology · 2018Article
- β-lactam/β-lactamase inhibitor combinations: an update.MedChemComm · 2018Review
- High adaptability of the omega loop underlies the substrate-spectrum-extension evolution of a class A β-lactamase, PenL.Scientific reports · 2016Article
- Crystal Structures of KPC-2 and SHV-1 β-Lactamases in Complex with the Boronic Acid Transition State Analog S02030.Antimicrobial agents and chemotherapy · 2016Article
- Boronic Acid Transition State Inhibitors Active against KPC and Other Class A β-Lactamases: Structure-Activity Relationships as a Guide to Inhibitor Design.Antimicrobial agents and chemotherapy · 2016Article
- Detecting a quasi-stable imine species on the reaction pathway of SHV-1 β-lactamase and 6β-(hydroxymethyl)penicillanic acid sulfone.Biochemistry · 2015Article
- Classification of Beta-lactamases and penicillin binding proteins using ligand-centric network models.PloS one · 2015Article
- Article
- New β-lactamase inhibitors: a therapeutic renaissance in an MDR world.Antimicrobial agents and chemotherapy · 2014Review
- Investigational antimicrobial agents of 2013.Clinical microbiology reviews · 2013Review
- Crystal structure of a preacylation complex of the β-lactamase inhibitor sulbactam bound to a sulfenamide bond-containing thiol-β-lactamase.Journal of the American Chemical Society · 2012Article
- Significant reduction in errors associated with nonbonded contacts in protein crystal structures: automated all-atom refinement with PrimeX.Acta crystallographica. Section D, Biological crystallography · 2012Article
- Crystal structures of KPC-2 β-lactamase in complex with 3-nitrophenyl boronic acid and the penam sulfone PSR-3-226.Antimicrobial agents and chemotherapy · 2012Article
- Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Boronic acid transition state inhibitors (BATSIs) are potent class A and C β-lactamase inactivators and are of particular interest due to their reversible nature mimicking the transition state. Here, we present structural and kinetic data describing the inhibition of the SHV-1 β-lactamase, a clinically important enzyme found in Klebsiella pneumoniae, by BATSI compounds possessing the R1 side chains of ceftazidime and cefoperazone and designed variants of the latter, compounds 1 and 2. The ceftazidime and cefoperazone BATSI compounds inhibit the SHV-1 β-lactamase with micromolar affinity that is considerably weaker than their inhibition of other β-lactamases. The solved crystal structures of these two BATSIs in complex with SHV-1 reveal a possible reason for SHV-1's relative resistance to inhibition, as the BATSIs adopt a deacylation transition state conformation compared to the usual acylation transition state conformation when complexed to other β-lactamases. Active-site comparison suggests that these conformational differences might be attributed to a subtle shift of residue A237 in SHV-1. The ceftazidime BATSI structure revealed that the carboxyl-dimethyl moiety is positioned in SHV-1's carboxyl binding pocket. In contrast, the cefoperazone BATSI has its R1 group pointing away from the active site such that its phenol moiety moves residue Y105 from the active site via end-on stacking interactions. To work toward improving the affinity of the cefoperazone BATSI, we synthesized two variants in which either one or two extra carbons were added to the phenol linker. Both variants yielded improved affinity against SHV-1, possibly as a consequence of releasing the strain of its interaction with the unusual Y105 conformation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.