ArticleAntimicrobial agents and chemotherapy2011
Distant and new mutations in CTX-M-1 beta-lactamase affect cefotaxime hydrolysis.
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 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Mapping the determinants of catalysis and substrate specificity of the antibiotic resistance enzyme CTX-M β-lactamase.Communications biology · 2023Article
- Significant role of Asn-247 and Arg-64 residues in close proximity of the active site in maintaining the catalytic function of CTX-M-15 type β-lactamase.RSC advances · 2019Article
- Synergistic effects of functionally distinct substitutions in β-lactamase variants shed light on the evolution of bacterial drug resistance.The Journal of biological chemistry · 2018Article
- Predicting allostery and microbial drug resistance with molecular simulations.Current opinion in structural biology · 2018Review
- Defining Substrate Specificity in the CTX-M Family: the Role of Asp240 in Ceftazidime Hydrolysis.Antimicrobial agents and chemotherapy · 2018Article
- Functional Characterization of CTX-M-14 and CTX-M-15 β-Lactamases byAntimicrobial agents and chemotherapy · 2017Article
- Predicting allosteric mutants that increase activity of a major antibiotic resistance enzyme.Chemical science · 2017Article
- The Drug-Resistant Variant P167S Expands the Substrate Profile of CTX-M β-Lactamases for Oxyimino-Cephalosporin Antibiotics by Enlarging the Active Site upon Acylation.Biochemistry · 2017Article
- Synergistic Effect of Doripenem and Cefotaxime to Inhibit CTX-M-15 Type β-Lactamases: Biophysical and Microbiological Views.Frontiers in pharmacology · 2017Article
- Excess positional mutual information predicts both local and allosteric mutations affecting beta lactamase drug resistance.Bioinformatics (Oxford, England) · 2016Article
- A Mechanism of Synergistic Effect of Streptomycin and Cefotaxime on CTX-M-15 Type β-lactamase Producing Strain ofFrontiers in microbiology · 2016Article
- bla CTX-M-152, a Novel Variant of CTX-M-group-25, Identified in a Study Performed on the Prevalence of Multidrug Resistance among Natural Inhabitants of River Yamuna, India.Frontiers in microbiology · 2016Article
- Biochemical characterization of CTX-M-15 from Enterobacter cloacae and designing a novel non-β-lactam-β-lactamase inhibitor.PloS one · 2013Article
- GES-18, a new carbapenem-hydrolyzing GES-Type β-lactamase from Pseudomonas aeruginosa that contains Ile80 and Ser170 residues.Antimicrobial agents and chemotherapy · 2013Article
- CTX-M Enzymes: Origin and Diffusion.Frontiers in microbiology · 2012Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CTX-M β-lactamases are an increasingly prevalent group of extended-spectrum β-lactamases (ESBL). Point mutations in CTX-M β-lactamases are considered critical for enhanced hydrolysis of cefotaxime. In order to clarify the structural determinants of the activity against cefotaxime in CTX-M β-lactamases, screening for random mutations was carried out to search for decreased activity against cefotaxime, with the CTX-M-1 gene as a model. Thirteen single mutants with a considerable reduction in cefotaxime MICs were selected for biochemical and stability studies. The 13 mutated genes of the CTX-M-1 β-lactamase were expressed, and the proteins were purified for kinetic studies against cephalothin and cefotaxime (as the main antibiotics). Some of the positions, such as Val103Asp, Asn104Asp, Asn106Lys, and Pro107Ser, are located in the (103)VNYN(106) loop, which had been described as important in cefotaxime hydrolysis, although this has not been experimentally confirmed. There are four mutations located close to catalytic residues-Thr71Ile, Met135Ile, Arg164His, and Asn244Asp-that may affect the positioning of these residues. We show here that some distant mutations, such as Ala219Val, are critical for cefotaxime hydrolysis and highlight the role of this loop at the top of the active site. Other distant substitutions, such as Val80Ala, Arg191, Ala247Ser, and Val260Leu, are in hydrophobic cores and may affect the dynamics and flexibility of the enzyme. We describe here, in conclusion, new residues involved in cefotaxime hydrolysis in CTX-M β-lactamases, five of which are in positions distant from the catalytic center.
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