ArticleAntimicrobial agents and chemotherapy2017
Active-Site Protonation States in an Acyl-Enzyme Intermediate of a Class A β-Lactamase with a Monobactam Substrate.
Article in Antimicrobial agents and chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Simultaneous enhancement of multiple functional properties using evolution-informed protein design.Nature communications · 2024Article
- 3D-QSAR, ADMET, and molecular docking studies of aztreonam analogs asSAGE open medicine · 2024Article
- Simultaneous enhancement of multiple functional properties using evolution-informed protein design.bioRxiv : the preprint server for biology · 2023Article
- 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
- Mutation of the conserved Asp-Asp pair impairs the structure, function, and inhibition of CTX-M Class A β-lactamase.FEBS letters · 2021Article
- Metallo-β-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design.Chemical reviews · 2021Review
- Study on Demethoxycurcumin as a Promising Approach to Reverse Methicillin-Resistance ofInternational journal of molecular sciences · 2021Article
- Structural Basis and Binding Kinetics of Vaborbactam in Class A β-Lactamase Inhibition.Antimicrobial agents and chemotherapy · 2020Article
- Mechanism of proton transfer in class A β-lactamase catalysis and inhibition by avibactam.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- β-Lactamase of Mycobacterium tuberculosis Shows Dynamics in the Active Site That Increase upon Inhibitor Binding.Antimicrobial agents and chemotherapy · 2020Article
- Probing the role of the conserved residue Glu166 in a class A β-lactamase using neutron and X-ray protein crystallography.Acta crystallographica. Section D, Structural biology · 2020Article
- Structural Insights into the Inhibition of the Extended-Spectrum β-Lactamase PER-2 by Avibactam.Antimicrobial agents and chemotherapy · 2019Article
- β-Lactamases and β-Lactamase Inhibitors in the 21st Century.Journal of molecular biology · 2019Review
- Molecular Insights on the Release of Avibactam from the Acyl-Enzyme Complex.Biophysical journal · 2019Article
- The rise of neutron cryo-crystallography.Acta crystallographica. Section D, Structural biology · 2018Review
- Optimizing Crystal Size of Photosystem II by Macroseeding: Toward Neutron Protein Crystallography.Crystal growth & design · 2018Article
- Crystallographic Snapshots of Class A β-Lactamase Catalysis Reveal Structural Changes That Facilitate β-Lactam Hydrolysis.The Journal of biological chemistry · 2017Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The monobactam antibiotic aztreonam is used to treat cystic fibrosis patients with chronic pulmonary infections colonized by Pseudomonas aeruginosa strains expressing CTX-M extended-spectrum β-lactamases. The protonation states of active-site residues that are responsible for hydrolysis have been determined previously for the apo form of a CTX-M β-lactamase but not for a monobactam acyl-enzyme intermediate. Here we used neutron and high-resolution X-ray crystallography to probe the mechanism by which CTX-M extended-spectrum β-lactamases hydrolyze monobactam antibiotics. In these first reported structures of a class A β-lactamase in an acyl-enzyme complex with aztreonam, we directly observed most of the hydrogen atoms (as deuterium) within the active site. Although Lys 234 is fully protonated in the acyl intermediate, we found that Lys 73 is neutral. These findings are consistent with Lys 73 being able to serve as a general base during the acylation part of the catalytic mechanism, as previously proposed.
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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.