ArticleThe Journal of biological chemistry
Natural variants modify Klebsiella pneumoniae carbapenemase (KPC) acyl-enzyme conformational dynamics to extend antibiotic resistance.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
- Dynamical-nonequilibrium alanine scanning for identifying allosteric positions in proteins.Biophysical journal · 2026Article
- Cefdinir binding to a class A β-lactamase revealed by serial cryo-crystallography.Acta crystallographica. Section D, Structural biology · 2026Article
- Carbapenemases: epidemiology, detection and management in a changing global landscape.JAC-antimicrobial resistance · 2026Review
- Genetic diversity and occurrence of antibiotic resistance genes from community wastewater in Dhaka and Cox's Bazar, Bangladesh.One health (Amsterdam, Netherlands) · 2026Article
- Role of Ambler Position 104 in Defining Substrate Specificity in the KPC Family of β-Lactamases.ACS infectious diseases · 2026Article
- Reduced catalytic activity of KPC β-lactamase can increase ceftazidime resistance.Communications biology · 2026Article
- Cryptic phenotypic variation emerges rapidly during the adaptive evolution of a carbapenemase.Nature ecology & evolution · 2026Article
- Unveiling structural dynamics and allosteric vulnerabilities in Klebsiella pneumoniae KPHS_11890: an integrated DRKG-MD study.Journal of computer-aided molecular design · 2025Article
- Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Impact of the double deletion ΔG242-T243 in KPC-2 in the effectiveness of ceftazidime-avibactam and imipenem-relebactam.Antimicrobial agents and chemotherapy · 2025Article
- Spectrum of cefepime-taniborbactam coverage against 190 β-lactamases defined in engineered isogenicAntimicrobial agents and chemotherapy · 2025Article
- Evolution ofJournal of Korean medical science · 2024Article
- Multilevel superposition for deciphering the conformational variability of protein ensembles.Briefings in bioinformatics · 2024Article
- The mechanism of ceftazidime and cefiderocol hydrolysis by D179Y variants of KPC carbapenemases is similar and involves the formation of a long-lived covalent intermediate.Antimicrobial agents and chemotherapy · 2024Article
- Drug Discovery in the Field of β-Lactams: An Academic Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- TheAntibiotics (Basel, Switzerland) · 2023Article
- Genotypic Evolution of Klebsiella pneumoniae Sequence Type 512 during Ceftazidime/Avibactam, Meropenem/Vaborbactam, and Cefiderocol Treatment, Italy.Emerging infectious diseases · 2023Article
- Aromatic Diboronic Acids as Effective KPC/AmpC Inhibitors.Molecules (Basel, Switzerland) · 2023Article
- Exploring avibactam and relebactam inhibition ofAntimicrobial agents and chemotherapy · 2023Article
- Synthesis of a Novel Boronic Acid Transition State Inhibitor, MB076: A Heterocyclic Triazole Effectively InhibitsJournal of medicinal chemistry · 2023Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Class A serine β-lactamases (SBLs) are key antibiotic resistance determinants in Gram-negative bacteria. SBLs neutralize β-lactams via a hydrolytically labile covalent acyl-enzyme intermediate. Klebsiella pneumoniae carbapenemase (KPC) is a widespread SBL that hydrolyzes carbapenems, the most potent β-lactams; known KPC variants differ in turnover of expanded-spectrum oxyimino-cephalosporins (ESOCs), for example, cefotaxime and ceftazidime. Here, we compare ESOC hydrolysis by the parent enzyme KPC-2 and its clinically observed double variant (P104R/V240G) KPC-4. Kinetic analyses show that KPC-2 hydrolyzes cefotaxime more efficiently than the bulkier ceftazidime, with improved ESOC turnover by KPC-4 resulting from enhanced turnover (k
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