Inactive-to-Active Transition of Human Thymidine Kinase 1 Revealed by Molecular Dynamics Simulations.

ABSTRACT: Despite its importance in the nucleoside (and nucleoside prodrug) metabolism, the structure of the active conformation of human thymidine kinase 1 (hTK1) remains elusive. We perform microsecond molecular dynamics simulations of the inactive enzyme form bound to a bisubstrate inhibitor that was shown experimentally to activate another TK1-like kinase, Thermotoga maritima TK (TmTK). Our results are in excellent agreement with the experimental findings for the TmTK closed-to-open state transition. We show that the inhibitor induces an increase of the enzyme radius of gyration due to the expansion on one of the dimer interfaces; the structural changes observed, including the active site pocket volume increase and the decrease in the monomer-monomer buried surface area and

SUBMITTER: Makurat S 

PROVIDER: S-EPMC8757434 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature