ArticleBiochemistry2015
Molecular basis for the catalytic specificity of the CTX-M extended-spectrum β-lactamases.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 54 citations in OpenAlex.
- Cefdinir binding to a class A β-lactamase revealed by serial cryo-crystallography.Acta crystallographica. Section D, Structural biology · 2026Article
- Epidemiology and Molecular Profiles of ESBL-ProducingMicroorganisms · 2026Article
- Molecular detection of CTX-M ESBL-encoding genes inOpen veterinary journal · 2026Article
- Phosphate sensitivity of KPC-2: a hidden variable in β-lactamase kinetics.Antimicrobial agents and chemotherapy · 2026Article
- Molecular insights into antimicrobial resistance in human bacterial pathogens: mechanisms, resistance genes, and translational diagnostic applications.Frontiers in microbiology · 2026Review
- Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Sodium ibuprofenate: antibacterial activities and potential β-lactamase inhibition in critical Gram-negative bacteria.Future microbiology · 2025Article
- β-Lactamase and Macrolide Resistance Gene Carriage inOpen forum infectious diseases · 2024Article
- Network of epistatic interactions in an enzyme active site revealed by large-scale deep mutational scanning.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Toward physics-based precision medicine: Exploiting protein dynamics to design new therapeutics and interpret variants.Protein science : a publication of the Protein Society · 2024Review
- Prevalence of extended spectrum beta lactamase and molecular detection of blaTEM, blaSHV and blaCTX-M genotypes among Gram negative bacilli isolates from pediatric patient population in Gaza strip.BMC infectious diseases · 2023Article
- Mapping the determinants of catalysis and substrate specificity of the antibiotic resistance enzyme CTX-M β-lactamase.Communications biology · 2023Article
- Antimicrobial Susceptibility and Genetic Prevalence of Extended-Spectrum β-Lactamases in Gram-Negative Rods Isolated from Clinical Specimens in Pakistan.Antibiotics (Basel, Switzerland) · 2022Article
- Functional Dynamics of Substrate Recognition in TEM Beta-Lactamase.Entropy (Basel, Switzerland) · 2022Article
- QM/MM modeling of class A β-lactamases reveals distinct acylation pathways for ampicillin and cefalexin.Organic & biomolecular chemistry · 2021Article
- Brief survey on organometalated antibacterial drugs and metal-based materials with antibacterial activity.RSC chemical biology · 2021Review
- Whole Genome Sequencing of Extended-Spectrum- and AmpC- β-Lactamase-Positive Enterobacterales Isolated From Spinach Production in Gauteng Province, South Africa.Frontiers in microbiology · 2021Article
- A drug-resistant β-lactamase variant changes the conformation of its active-site proton shuttle to alter substrate specificity and inhibitor potency.The Journal of biological chemistry · 2020Article
- Multidrug-Resistant CTX-M and CMY-2 ProducingMicrobial drug resistance (Larchmont, N.Y.) · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Extended-spectrum β-lactamases (ESBLs) pose a threat to public health because of their ability to confer resistance to extended-spectrum cephalosporins such as cefotaxime. The CTX-M β-lactamases are the most widespread ESBL enzymes among antibiotic resistant bacteria. Many of the active site residues are conserved between the CTX-M family and non-ESBL β-lactamases such as TEM-1, but the residues Ser237 and Arg276 are specific to the CTX-M family, suggesting that they may help to define the increased specificity for cefotaxime hydrolysis. To test this hypothesis, site-directed mutagenesis of these positions was performed in the CTX-M-14 β-lactamase. Substitutions of Ser237 and Arg276 with their TEM-1 counterparts, Ala237 and Asn276, had a modest effect on cefotaxime hydrolysis, as did removal of the Arg276 side chain in an R276A mutant. The S237A:R276N and S237A:R276A double mutants, however, exhibited 29- and 14-fold losses in catalytic efficiency for cefotaxime hydrolysis, respectively, while the catalytic efficiency for benzylpenicillin hydrolysis was unchanged. Therefore, together, the Ser237 and Arg276 residues are important contributors to the cefotaximase substrate profile of the enzyme. High-resolution crystal structures of the CTX-M-14 S70G, S70G:S237A, and S70G:S237A:R276A variants alone and in complex with cefotaxime show that residues Ser237 and Arg276 in the wild-type enzyme promote the expansion of the active site to accommodate cefotaxime and favor a conformation of cefotaxime that allows optimal contacts between the enzyme and substrate. The conservation of these residues, linked to their effects on structure and catalysis, imply that their coevolution is an important specificity determinant in the CTX-M family.
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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.