ArticleeLife2021
Allosteric communication in class A β-lactamases occurs via cooperative coupling of loop dynamics.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Dynamical-nonequilibrium alanine scanning for identifying allosteric positions in proteins.Biophysical journal · 2026Article
- Directional information flow as a tool for analyzing protein allostery.bioRxiv : the preprint server for biology · 2026Article
- Deep learning insights into β-lactamase dynamics and resistance evolution.The Biochemical journal · 2026Review
- Role of Ambler Position 104 in Defining Substrate Specificity in the KPC Family of β-Lactamases.ACS infectious diseases · 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
- Identification and understanding of allostery hotspots in proteins: Integration of deep mutational scanning and multi-faceted computational analyses.Journal of molecular biology · 2025Review
- Sparse networks of conformational fluctuations communicate signals within proteins.bioRxiv : the preprint server for biology · 2025Article
- Novel C5α-substituted carbapenems enhanceAntimicrobial agents and chemotherapy · 2025Article
- Molecular Fingerprint of Cold Adaptation in Antarctic Icefish PepT1 (Biomolecules · 2025Article
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- Breakthrough Advances in Beta-Lactamase Inhibitors: New Synthesized Compounds and Mechanisms of Action Against Drug-Resistant Bacteria.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Molecular mechanisms responsible KPC-135-mediated resistance to ceftazidime-avibactam in ST11-K47 hypervirulentEmerging microbes & infections · 2024Article
- Friends and relatives: insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN.Faraday discussions · 2024Article
- Signal Propagation in the ATPase Domain ofBiochemistry · 2024Article
- Deciphering the Coevolutionary Dynamics of L2 β-Lactamases via Deep Learning.Journal of chemical information and modeling · 2024Article
- Nuclear receptor interdomain communication is mediated by the hinge with ligand specificity.bioRxiv : the preprint server for biology · 2024Article
- 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
- Multilevel superposition for deciphering the conformational variability of protein ensembles.Briefings in bioinformatics · 2024Article
- Modulation of Allostery with Multiple Mechanisms by Hotspot Mutations in TetR.Journal of the American Chemical Society · 2024Article
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Authors and funding
13 authors.
Funding
Abstract
Understanding allostery in enzymes and tools to identify it offer promising alternative strategies to inhibitor development. Through a combination of equilibrium and nonequilibrium molecular dynamics simulations, we identify allosteric effects and communication pathways in two prototypical class A β-lactamases, TEM-1 and KPC-2, which are important determinants of antibiotic resistance. The nonequilibrium simulations reveal pathways of communication operating over distances of 30 Å or more. Propagation of the signal occurs through cooperative coupling of loop dynamics. Notably, 50% or more of clinically relevant amino acid substitutions map onto the identified signal transduction pathways. This suggests that clinically important variation may affect, or be driven by, differences in allosteric behavior, providing a mechanism by which amino acid substitutions may affect the relationship between spectrum of activity, catalytic turnover, and potential allosteric behavior in this clinically important enzyme family. Simulations of the type presented here will help in identifying and analyzing such differences.
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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.