Related Experiment Video
Updated: Mar 28, 2026
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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Cryptic Binding Pockets in PDC‑3 β‑Lactamase Modulate Resistance Profiles
Shuang Chen1, Fedaa Attana1,2, Andrea M Hujer3
1UCL School of Pharmacy, London WC1N 1AX, U.K.
JACS Au
|March 27, 2026
Summary
Researchers mapped protein conformational changes using deep learning. They discovered a hidden pocket in PDC-3 beta-lactamase, offering a new target for drug development to combat antibiotic resistance.
Area of Science:
- Biochemistry
- Structural Biology
- Computational Biology
Background:
- Cryptic binding pockets in proteins influence crucial functions like catalysis and allostery.
- These pockets are often missed by experimental methods and standard molecular dynamics simulations.
Purpose of the Study:
- To map the complete conformational landscape of the Ω-loop in class C β-lactamase PDC-3.
- To identify novel cryptic pockets and understand their role in enzyme regulation and drug targeting.
Main Methods:
- Integration of enhanced sampling techniques with an unsupervised deep-learning pipeline.
- Analysis of protein conformational ensembles and molecular interactions.
Main Results:
- Identified three distinct conformational states: crystal-like, expansive, and constricted.
- Residues 219 and 221 function as molecular switches controlling enzyme states and resistance profiles.
- Discovered a previously hidden cryptic pocket upon catalytic site occlusion, suggesting an allosteric target.
Conclusions:
- The study presents a generalizable framework for uncovering hidden protein conformations and regulatory mechanisms.
- The identified cryptic pocket in PDC-3 presents a novel allosteric target for developing inhibitors to combat antibiotic resistance.
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