Solution Ionic Strength Can Modulate Functional Loop Conformations in E. coli Dihydrofolate Reductase.

ABSTRACT: The observation of multiple conformations of a functional loop (termed M20) in the Escherichia coli dihydrofolate reductase (ecDHFR) enzyme triggered the proposition that large-scale motions of protein structural elements contribute to enzyme catalysis. The transition of the M20 loop from a closed conformation to an occluded conformation was thought to aid the rate-limiting release of the products. However, the influence of charged species in the solution environment on the observed M20 loop conformations, independent of charged ligands bound to the enzyme, had not been considered. Molecular dynamics simulations of ecDHFR in model CaCl₂ solutions of varying molar ionic strengths I^M reveal a substantial free energy barrier betw

SUBMITTER: Babu CS 

PROVIDER: S-EPMC11075089 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature