ArticleScientific reports2020
The hydrolytic water molecule of Class A β-lactamase relies on the acyl-enzyme intermediate ES* for proper coordination and catalysis.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- A Single Substitution of Valine to Glutamic Acid in the Omega-Like Loop Introduces a Penicillinase-Like Activity in MSMEG_6194 by Compromising its Role as DD-Carboxypeptidase.Current microbiology · 2026Article
- Article
- It started off as a Cys, how did it end up like this? Identifying the extent of unmodelled oxidatively modified cysteines within the Protein Data Bank.Acta crystallographica. Section D, Structural biology · 2026Article
- Functional dynamics of water in New Delhi metallo-β-lactamase catalysis.Protein science : a publication of the Protein Society · 2026Article
- Clinically Significant Carbapenemases in Gram-Negative Pathogens: Molecular Diversity and Advances in β-Lactamase Inhibitor Therapy.Antibiotics (Basel, Switzerland) · 2026Review
- Characterization of the novel class A β-Lactamase gene blaBMC microbiology · 2026Article
- Saturation mutagenesis map of generalist versus specialist adaptations of β-lactamase to novel antibiotics.bioRxiv : the preprint server for biology · 2026Article
- Contrasting pH optima of β-lactamases CTX-M and CMY influenceApplied and environmental microbiology · 2026Article
- Structural insights into the activity of carbapenemases: understanding the mechanism of action of current inhibitors and informing the design of new carbapenem adjuvants.RSC medicinal chemistry · 2025Review
- Directed evolution of a beta-lactamase samples a wide variety of conformational states.Protein science : a publication of the Protein Society · 2025Article
- Review
- First-Genome Sequence Data of an Alcaligenes nematophilus Strain EBU-23 Encoding bla Gene Implicated in Acute Childhood Gastroenteritis.Current microbiology · 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
- Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Novel Antimicrobial Agents for Gram-Negative Pathogens.Antibiotics (Basel, Switzerland) · 2023Review
- Mapping the determinants of catalysis and substrate specificity of the antibiotic resistance enzyme CTX-M β-lactamase.Communications biology · 2023Article
- Chelation in Antibacterial Drugs: From Nitroxoline to Cefiderocol and Beyond.Antibiotics (Basel, Switzerland) · 2022Review
- QM/MM Simulations Reveal the Determinants of Carbapenemase Activity in Class A β-Lactamases.ACS infectious diseases · 2022Article
- The biogenesis of β-lactamase enzymes.Microbiology (Reading, England) · 2022Review
- Three new inhibitors of class A β-lactamases evaluated by molecular docking and dynamics simulations methods: relebactam, enmetazobactam, and QPX7728.Journal of molecular modeling · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serine-based β-lactamases of Class A, C and D all rely on a key water molecule to hydrolyze and inactivate β-lactam antibiotics. This process involves two conserved catalytic steps. In the first acylation step, the β-lactam antibiotic forms an acyl-enzyme intermediate (ES*) with the catalytic serine residue. In the second deacylation step, an activated water molecule serves as nucleophile (WAT_Nu) to attack ES* and release the inactivated β-lactam. The coordination and activation of WAT_Nu is not fully understood. Using time-resolved x-ray crystallography and QM/MM simulations, we analyzed three intermediate structures of Class A β-lactamase PenP as it slowly hydrolyzed cephaloridine. WAT_Nu is centrally located in the apo structure but becomes slightly displaced away by ES* in the post-acylation structure. In the deacylation structure, WAT_Nu moves back and is positioned along the Bürgi-Dunitz trajectory with favorable energetic profile to attack ES*. Unexpectedly, WAT_Nu is also found to adopt a catalytically incompetent conformation in the deacylation structure forming a hydrogen bond with ES*. Our results reveal that ES* plays a significant role in coordinating and activating WAT_Nu through subtle yet distinct interactions at different stages of the catalytic process. These interactions may serve as potential targets to circumvent β-lactamase-mediated antibiotic resistance.
Indexed as
Identifiers
What OpenQuestion holds
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.