ArticleJournal of medicinal chemistry2013
Design and exploration of novel boronic acid inhibitors reveals important interactions with a clavulanic acid-resistant sulfhydryl-variable (SHV) β-lactamase.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Exploration of novel β-lactamase inhibitors against Klebsiella pneumoniae using fragment-based drug discovery approach.Molecular diversity · 2026Article
- 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
- Exploring avibactam and relebactam inhibition ofAntimicrobial agents and chemotherapy · 2023Article
- Mutation of the conserved Asp-Asp pair impairs the structure, function, and inhibition of CTX-M Class A β-lactamase.FEBS letters · 2021Article
- Two β-Lactamase Variants with Reduced Clavulanic Acid Inhibition Display Different Millisecond Dynamics.Antimicrobial agents and chemotherapy · 2021Article
- Assessing the Potency of β-Lactamase Inhibitors with Diverse Inactivation Mechanisms against the PenA1 Carbapenemase fromACS infectious diseases · 2021Article
- Development of an Antibiotic Resistance Breaker to Resensitize Drug-ResistantFrontiers in cellular and infection microbiology · 2021Article
- A Genotype-Phenotype Correlation Study of SHV β-Lactamases Offers New Insight into SHV Resistance Profiles.Antimicrobial agents and chemotherapy · 2020Article
- Nacubactam Enhances Meropenem Activity against Carbapenem-Resistant Klebsiella pneumoniae Producing KPC.Antimicrobial agents and chemotherapy · 2019Article
- Beyond Piperacillin-Tazobactam: Cefepime and AAI101 as a Potent β-Lactam-β-Lactamase Inhibitor Combination.Antimicrobial agents and chemotherapy · 2019Article
- Article
- Characterization of the AmpC β-Lactamase from Burkholderia multivorans.Antimicrobial agents and chemotherapy · 2018Article
- Article
- Exposing a β-Lactamase "Twist": the Mechanistic Basis for the High Level of Ceftazidime Resistance in the C69F Variant of the Burkholderia pseudomallei PenI β-Lactamase.Antimicrobial agents and chemotherapy · 2016Article
- SHV-129: A Gateway to Global Suppressors in the SHV β-Lactamase Family?Molecular biology and evolution · 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
- Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli containing KPC and SHV β-lactamases with single amino acid substitutions in the Ω-loop.The Journal of antimicrobial chemotherapy · 2015Article
- Click Chemistry in Lead Optimization of Boronic Acids as β-Lactamase Inhibitors.Journal of medicinal chemistry · 2015Article
- Variants of β-lactamase KPC-2 that are resistant to inhibition by avibactam.Antimicrobial agents and chemotherapy · 2015Article
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14 authors.
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Abstract
Inhibitor resistant (IR) class A β-lactamases pose a significant threat to many current antibiotic combinations. The K234R substitution in the SHV β-lactamase, from Klebsiella pneumoniae , results in resistance to ampicillin/clavulanate. After site-saturation mutagenesis of Lys-234 in SHV, microbiological and biochemical characterization of the resulting β-lactamases revealed that only -Arg conferred resistance to ampicillin/clavulanate. X-ray crystallography revealed two conformations of Arg-234 and Ser-130 in SHV K234R. The movement of Ser-130 is the principal cause of the observed clavulanate resistance. A panel of boronic acid inhibitors was designed and tested against SHV-1 and SHV K234R. A chiral ampicillin analogue was discovered to have a 2.4 ± 0.2 nM K(i) for SHV K234R; the chiral ampicillin analogue formed a more complex hydrogen-bonding network in SHV K234R vs SHV-1. Consideration of the spatial position of Ser-130 and Lys-234 and this hydrogen-bonding network will be important in the design of novel antibiotics targeting IR β-lactamases.
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