The role of the Met²⁰ loop in the hydride transfer in Escherichia coli dihydrofolate reductase.

ABSTRACT: A key question concerning the catalytic cycle of Escherichia coli dihydrofolate reductase (ecDHFR) is whether the Met²⁰ loop is dynamically coupled to the chemical step during catalysis. A more basic, yet unanswered question is whether the Met²⁰ loop adopts a closed conformation during the chemical hydride transfer step. To examine the most likely conformation of the Met²⁰ loop during the chemical step, we studied the hydride transfer in wild type (WT) ecDHFR using hybrid quantum mechanics-molecular mechanics free energy simulations with the Met²⁰ loop in a closed and disordered conformation. Additionally, we investigated three mutant forms (I14X; X = Val, Ala, Gly) of the enzyme that have increased active site

SUBMITTER: Mhashal AR 

PROVIDER: S-EPMC5572915 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature