ArticleJournal of the American Chemical Society2022
Protein Electric Fields Enable Faster and Longer-Lasting Covalent Inhibition of β-Lactamases.
Article in Journal of the American Chemical Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- Environmental and mutational modulation of collateral fitness effects informs their mechanisms.Molecular biology and evolution · 2026Article
- Structural perspectives on clinical β-lactamase inhibitors: From mechanism to resistance.Journal of microbiology (Seoul, Korea) · 2026Review
- Electric Fields Can Assist Prebiotic Reactivity on Hydrogen Cyanide Surfaces.ACS central science · 2026Article
- Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Electrostatic atlas of non-covalent interactions built into metal-organic frameworks.Nature chemistry · 2025Article
- Covalent Ligand Electrophiles Are Differentially Activated by Proximity Effects Which Govern Latent Protein Reactivity.ACS central science · 2025Article
- Preorganized Electric Fields in Voltage-Gated Sodium Channels.Chembiochem : a European journal of chemical biology · 2025Article
- Deciphering multi-dimensional interfacial mechanisms via organic cosolvent engineering for sustainable zinc metal batteries.Nature communications · 2025Article
- Hydrogen Bond Blueshifts in Nitrile Vibrational Spectra Are Dictated by Hydrogen Bond Geometry and Dynamics.JACS Au · 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
- An Ion-Pair Induced Intermediate Complex Captured in Class D Carbapenemase Reveals Chloride Ion as a Janus Effector Modulating Activity.ACS central science · 2023Article
- Direct measurements of biomolecular electrostatics through experiments.Current opinion in structural biology · 2023Review
- High-throughput computational investigation of protein electrostatics and cavity for SAM-dependent methyltransferases.Protein science : a publication of the Protein Society · 2023Article
- β-Lactamases Evolve against Antibiotics by Acquiring Large Active-Site Electric Fields.Journal of the American Chemical Society · 2022Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
The widespread design of covalent drugs has focused on crafting reactive groups of proper electrophilicity and positioning toward targeted amino-acid nucleophiles. We found that environmental electric fields projected onto a reactive chemical bond, an overlooked design element, play essential roles in the covalent inhibition of TEM-1 β-lactamase by avibactam. Using the vibrational Stark effect, the magnitudes of the electric fields that are exerted by TEM active sites onto avibactam's reactive C═O were measured and demonstrate an electrostatic gating effect that promotes bond formation yet relatively suppresses the reverse dissociation. These results suggest new principles of covalent drug design and off-target site prediction. Unlike shape and electrostatic complementary which address binding constants, electrostatic catalysis drives reaction rates, essential for covalent inhibition, and deepens our understanding of chemical reactivity, selectivity, and stability in complex systems.
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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.