Local Xenon-Protein Interaction Produces Global Conformational Change and Allosteric Inhibition in Lysozyme.

ABSTRACT: Noble gases have well-established biological effects, yet their molecular mechanisms remain poorly understood. Here, we investigated, both experimentally and computationally, the molecular modes of xenon (Xe) action in bacteriophage T4 lysozyme (T4L). By combining indirect gassing methods with a colorimetric lysozyme activity assay, a reversible, Xe-specific (20 ± 3)% inhibition effect was observed. Accelerated molecular dynamic simulations revealed that Xe exerts allosteric inhibition on the protein by expanding a C-terminal hydrophobic cavity. Xe-induced cavity expansion results in global conformational changes, with long-range transduction distorting the active site where peptidoglycan binds. Interestingly, the peptide substrate binding site that enables lysozyme specificity does not ch

SUBMITTER: He J 

PROVIDER: S-EPMC10821772 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature