ArticleAntimicrobial agents and chemotherapy2010
Comparative biochemical and computational study of the role of naturally occurring mutations at Ambler positions 104 and 170 in GES β-lactamases.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Evaluation of carbapenem inactivation method-based phenotypic assays for the detection of GES-type carbapenemases in Enterobacterales,Journal of clinical microbiology · 2026Article
- Phylogenetic predictions of carbapenemase activity from the Guiana extended-spectrum (GES) family of β-lactamases.JAC-antimicrobial resistance · 2024Article
- High Prevalence of GES-5 Variant and Co-Expression of VIM-2 and GES-45 among ClinicalAntibiotics (Basel, Switzerland) · 2023Article
- Unveiling the structural features that regulate carbapenem deacylation in KPC-2 through QM/MM and interpretable machine learning.Physical chemistry chemical physics : PCCP · 2023Article
- Detection of carbapenemase producing enterobacteria using an ion sensitive field effect transistor sensor.Scientific reports · 2021Article
- Molecular Characterization of Class 1, 2 and 3 Integrons inInfection and drug resistance · 2021Article
- A Novel, Integron-Regulated, Class C β-Lactamase.Antibiotics (Basel, Switzerland) · 2020Article
- Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales.Frontiers in medicine · 2020Review
- Sewage effluent from an Indian hospital harbors novel carbapenemases and integron-borne antibiotic resistance genes.Microbiome · 2019Article
- Acquisition of Extended-Spectrum β-Lactamase GES-6 Leading to Resistance to Ceftolozane-Tazobactam Combination inAntimicrobial agents and chemotherapy · 2019Article
- Prevalence of ESBL-producing Pseudomonas aeruginosa isolates in Warsaw, Poland, detected by various phenotypic and genotypic methods.PloS one · 2017Article
- Kinetic characterization of GES-22 β-lactamase harboring the M169L clinical mutation.The Journal of antibiotics · 2016Article
- Complete Nucleotide Sequence of IncP-1β Plasmid pDTC28 Reveals a Non-Functional Variant of the blaGES-Type Gene.PloS one · 2016Article
- Structural and Functional Aspects of Class A Carbapenemases.Current drug targets · 2016Review
- Genetic and Biochemical Characterization of FRI-1, a Carbapenem-Hydrolyzing Class A β-Lactamase from Enterobacter cloacae.Antimicrobial agents and chemotherapy · 2015Article
- In vitro prediction of the evolution of GES-1 β-lactamase hydrolytic activity.Antimicrobial agents and chemotherapy · 2015Article
- Osteomyelitis due to multiple carbapenemase-producing Gram-negative bacteria: The first case report of a GES-13-producing Pseudomonas aeruginosa isolate in Canada.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2014Article
- Structural analysis of the role of Pseudomonas aeruginosa penicillin-binding protein 5 in β-lactam resistance.Antimicrobial agents and chemotherapy · 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
- "Stormy waters ahead": global emergence of carbapenemases.Frontiers in microbiology · 2013Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In GES-type β-lactamases, positions 104 and 170 are occupied by Glu or Lys and by Gly, Asn, or Ser, respectively. Previous studies have indicated an important role of these amino acids in the interaction with β-lactams, although their precise role, especially that of residue 104, remains uncertain. In this study, we constructed GES-1 (Glu104, Gly170), GES-2 (Glu104, Asn170), GES-5 (Glu104, Ser170), GES-6 (Lys104, Ser170), GES-7 (Lys104, Gly170), and GES-13 (Lys104, Asn170) by site-specific mutagenesis and compared their hydrolytic properties. Isogenic comparisons of β-lactam resistance levels conferred by these GES variants were also performed. Data indicated the following patterns: (i) Lys104-containing enzymes exhibited enhanced hydrolysis of oxyimino-cephalosporins and reduced efficiency against imipenem in relation to enzymes possessing Glu104, (ii) Asn170-containing enzymes showed reduced hydrolysis rates of penicillins and older cephalosporins, (iii) Ser170 enabled GES to hydrolyze cefoxitin efficiently, and (iv) Asn170 and Ser170 increased the carbapenemase character of GES enzymes but reduced their activity against ceftazidime. Molecular dynamic simulations of GES apoenzyme models, as well as construction of GES structures complexed with cefoxitin and an achiral ceftazidime-like boronic acid, provided insights into the catalytic behavior of the studied mutants. There were indications that an increased stability of the hydrogen bonding network of Glu166-Lys73-Ser70 and an altered positioning of Trp105 correlated with the substrate spectra, especially with acylation of GES by imipenem. Furthermore, likely effects of Ser170 on GES interactions with cefoxitin and of Lys104 on interactions with oxyimino-cephalosporins were revealed. Overall, the data unveiled the importance of residues 104 and 170 in the function of GES enzymes.
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