ArticleBiochemistry2015
Kinetic and structural requirements for carbapenemase activity in GES-type 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 38 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Structural basis for carbapenem-hydrolyzing mechanisms of carbapenemases conferring antibiotic resistance.International journal of molecular sciences · 2015Pooled it
- Comparative evaluation of the activity of novel β-lactam antibiotics against difficult-to-treatJAC-antimicrobial resistance · 2026Article
- Carbapenemases: epidemiology, detection and management in a changing global landscape.JAC-antimicrobial resistance · 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
- Article
- Mechanistic basis for inhibition of the extended-spectrum β-lactamase GES-1 by enmetazobactam and tazobactam.FEBS letters · 2025Article
- Dual mechanism of the OXA-23 carbapenemase inhibition by the carbapenem NA-1-157.Antimicrobial agents and chemotherapy · 2025Article
- Article
- Article
- Restricted Rotational Flexibility of the C5α-Methyl-Substituted Carbapenem NA-1-157 Leads to Potent Inhibition of the GES-5 Carbapenemase.ACS infectious diseases · 2024Article
- Phylogenetic predictions of carbapenemase activity from the Guiana extended-spectrum (GES) family of β-lactamases.JAC-antimicrobial resistance · 2024Article
- Three separate acquisitions of blaEuropean journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023Article
- The C5α-Methyl-Substituted Carbapenem NA-1-157 Exhibits Potent Activity againstACS infectious diseases · 2023Article
- From Batch to the Semi-Continuous Flow Hydrogenation ofPharmaceutics · 2023Article
- Carbapenem Combinations for Infections Caused by Carbapenemase-ProducingAntibiotics (Basel, Switzerland) · 2022Article
- QM/MM Simulations Reveal the Determinants of Carbapenemase Activity in Class A β-Lactamases.ACS infectious diseases · 2022Article
- Article
- Imipenem/Relebactam Resistance in Clinical Isolates of Extensively Drug Resistant Pseudomonas aeruginosa: Inhibitor-Resistant β-Lactamases and Their Increasing Importance.Antimicrobial agents and chemotherapy · 2022Article
- KPC-3-, GES-5-, and VIM-1-ProducingInternational journal of environmental research and public health · 2022Article
- The Collateral Effects of COVID-19 Pandemic on the Status of Carbapenemase-Producing Pathogens.Frontiers in cellular and infection microbiology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Carbapenems are the last resort antibiotics for treatment of life-threatening infections. The GES β-lactamases are important contributors to carbapenem resistance in clinical bacterial pathogens. A single amino acid difference at position 170 of the GES-1, GES-2, and GES-5 enzymes is responsible for the expansion of their substrate profile to include carbapenem antibiotics. This highlights the increasing need to understand the mechanisms by which the GES β-lactamases function to aid in development of novel therapeutics. We demonstrate that the catalytic efficiency of the enzymes with carbapenems meropenem, ertapenem, and doripenem progressively increases (100-fold) from GES-1 to -5, mainly due to an increase in the rate of acylation. The data reveal that while acylation is rate limiting for GES-1 and GES-2 for all three carbapenems, acylation and deacylation are indistinguishable for GES-5. The ertapenem-GES-2 crystal structure shows that only the core structure of the antibiotic interacts with the active site of the GES-2 β-lactamase. The identical core structures of ertapenem, doripenem, and meropenem are likely responsible for the observed similarities in the kinetics with these carbapenems. The lack of a methyl group in the core structure of imipenem may provide a structural rationale for the increase in turnover of this carbapenem by the GES β-lactamases. Our data also show that in GES-2 an extensive hydrogen-bonding network between the acyl-enzyme complex and the active site water attenuates activation of this water molecule, which results in poor deacylation by this enzyme.
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Registered trials
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.