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Updated: Sep 21, 2025
08:06
The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
Published on: February 1, 2018
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Functional Dynamics of Substrate Recognition in TEM Beta-Lactamase.
Chris Avery1, Lonnie Baker1, Donald J Jacobs2
1Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
Entropy (Basel, Switzerland)
|May 28, 2022
Summary
Understanding TEM beta-lactamase enzyme dynamics is crucial for combating antibiotic resistance. This study reveals how mutations affect substrate recognition and identifies new targets for noncompetitive inhibitors to overcome resistance.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Beta-lactamase enzymes confer resistance to beta-lactam antibiotics.
- Extended-spectrum and inhibitor-resistant beta-lactamase mutants pose a significant global health threat.
Purpose of the Study:
- To investigate the functional dynamics controlling substrate recognition in TEM beta-lactamase.
- To compare wild-type and mutant TEM beta-lactamases in various states and antibiotic complexes.
- To identify allosteric mechanisms and functionally important conserved dynamics.
Main Methods:
- All-atom molecular dynamics simulations.
- Quasi-harmonic normal mode analysis with perturbation scan for dynamic allostery.
- Multivariate comparative analysis of molecular dynamics trajectories.
Main Results:
- Identified an allosteric mechanism inhibiting TEM beta-lactamase function and other allosteric binding targets.
- Elucidated substrate recognition mechanisms by analyzing dynamics changes due to mutations and ligand binding.
- Found that H10-H11 loop acts as a secondary anchor for extended-spectrum ligands, and H9-H10 loop stabilizes the protein.
Conclusions:
- Conserved dynamics are functionally important for substrate recognition in TEM beta-lactamase.
- Secondary non-catalytically-active loops (H10-H11 and H9-H10) are key to understanding enzyme function and resistance.
- These loops represent attractive targets for developing novel noncompetitive inhibitors against TEM beta-lactamase.
Keywords:
SPLOCbeta-lactam antibioticsbeta-lactamasedynamic allosteryfunctional dynamicsmachine learningmolecular dynamicsMore Related Videos
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