ArticleACS central science2021
The Interplay of Electrostatics and Chemical Positioning in the Evolution of Antibiotic Resistance in TEM β-Lactamases.
Article in ACS central science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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
18 citing papers in PubMed, 41 citations in OpenAlex.
- Electrostatic atlas of non-covalent interactions built into metal-organic frameworks.Nature chemistry · 2025Article
- Development of a nitric oxide-releasing cephalexin-based hybrid compound for enhanced antimicrobial efficacy and biofilm disruption.RSC medicinal chemistry · 2025Article
- Label-Free Detection of Virus-Membrane Interactions Using Surface-Enhanced Infrared Absorption (SEIRA) Spectroscopy.Angewandte Chemie (International ed. in English) · 2025Article
- Carbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumannii.Scientific reports · 2024Article
- Hydrogen Bond Blueshifts in Nitrile Vibrational Spectra Are Dictated by Hydrogen Bond Geometry and Dynamics.JACS Au · 2024Article
- The Evolution of the Acylation Mechanism inACS catalysis · 2024Article
- Dissecting Allosteric Mutations for Antibiotic Resistance by Time-Dependent Linear Response Theory.Journal of chemical theory and computation · 2024Article
- Electric Fields Are a Key Determinant of Carbapenemase Activity in Class A β-Lactamases.ACS catalysis · 2024Article
- Critical Evaluation of Polarizable and Nonpolarizable Force Fields for Proteins Using Experimentally Derived Nitrile Electric Fields.Journal of the American Chemical Society · 2024Article
- Epistasis arises from shifting the rate-limiting step during enzyme evolution of a β-lactamase.Nature catalysis · 2024Article
- Review
- Direct measurements of biomolecular electrostatics through experiments.Current opinion in structural biology · 2023Review
- Protein Dynamics and Enzymatic Catalysis.The journal of physical chemistry. B · 2023Review
- β-Lactamases Evolve against Antibiotics by Acquiring Large Active-Site Electric Fields.Journal of the American Chemical Society · 2022Article
- Design of novel cyanovirin-N variants by modulation of binding dynamics through distal mutations.eLife · 2022Article
- Protein Electric Fields Enable Faster and Longer-Lasting Covalent Inhibition of β-Lactamases.Journal of the American Chemical Society · 2022Article
- Solvent Organization and Electrostatics Tuned by Solute Electronic Structure: Amide versus Non-Amide Carbonyls.The journal of physical chemistry. B · 2022Article
- Nitrile Infrared Intensities Characterize Electric Fields and Hydrogen Bonding in Protic, Aprotic, and Protein Environments.Journal of the American Chemical Society · 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
3 authors at 1 institution in 1 country.
Funding
Abstract
The interplay of enzyme active site electrostatics and chemical positioning is important for understanding the origin(s) of enzyme catalysis and the design of novel catalysts. We reconstruct the evolutionary trajectory of TEM-1 β-lactamase to TEM-52 toward extended-spectrum activity to better understand the emergence of antibiotic resistance and to provide insights into the structure-function paradigm and noncovalent interactions involved in catalysis. Utilizing a detailed kinetic analysis and the vibrational Stark effect, we quantify the changes in rates and electric fields in the Michaelis and acyl-enzyme complexes for penicillin G and cefotaxime to ascertain the evolutionary role of electric fields to modulate function. These data are combined with MD simulations to interpret and quantify the substrate-dependent structural changes during evolution. We observe that this evolutionary trajectory utilizes a large preorganized electric field and substrate-dependent chemical positioning to facilitate catalysis. This governs the evolvability, substrate promiscuity, and protein fitness landscape in TEM β-lactamase antibiotic resistance.
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.