Free energy calculations elucidate substrate binding, gating mechanism, and tolerance-promoting mutations in herbicide target 4-hydroxyphenylpyruvate dioxygenase.

ABSTRACT: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) catalyzes the second reaction in the tyrosine catabolism and is linked to the production of cofactors plastoquinone and tocopherol in plants. This important biological role has put HPPD in the focus of current herbicide design efforts including the development of herbicide-tolerant mutants. However, the molecular mechanisms of substrate binding and herbicide tolerance have yet to be elucidated. In this work, we performed molecular dynamics simulations and free energy calculations to characterize active site gating by the C-terminal helix H11 in HPPD. We compared gating equilibria in Arabidopsis thaliana (At) and Zea mays (Zm) wild-type proteins retrieving the experimentally observed preferred orientations from the simulations. We investigated the

SUBMITTER: Schindler CEM 

PROVIDER: S-EPMC6511742 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature