English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Phenylalanine hydroxylase (PAH) is an iron enzyme catalyzing the oxidation of l-Phe to l-Tyr during phenylalanine catabolism. Dysfunction of PAH leads to the debilitating condition phenylketonuria (PKU), which prompted research into the structure and function of PAH over the last 50 years. Despite intensive study, there is no consensus on the atomistic details of the mechanism of O 2 binding and splitting by wild-type (WT) PAH and how it varies with PKU-inducing mutations, Arg158Gln and Glu280Lys. We studied structures involved in a proposed mechanism for the WT and mutants using extensive mixed quantum-classical molecular dynamics simulations. Simulations reveal a previously unobserved dynamic coupling between the active site and the mutation sites, suggesting how they can affect the catalytic performance of PAH. Furthermore, the effect of the coupling on the PAH structure agrees with and expands our understanding of the experimentally observed differences in activity between the WT and mutants.

Uncovered Dynamic Coupling Resolves the Ambiguous Mechanism of Phenylalanine Hydroxylase Oxygen Binding