Molecular Rationale for Partitioning between C-H and C-F Bond Activation in Heme-Dependent Tyrosine Hydroxylase.

ABSTRACT: The heme-dependent l-tyrosine hydroxylases (TyrHs) in natural product biosynthesis constitute a new enzyme family in contrast to the nonheme iron enzymes for DOPA production. A representative TyrH exhibits dual reactivity of C-H and C-F bond cleavage when challenged with 3-fluoro-l-tyrosine (3-F-Tyr) as a substrate. However, little is known about how the enzyme mediates two distinct reactions. Herein, a new TyrH from the thermophilic bacterium Streptomyces sclerotialus (SsTyrH) was functionally and structurally characterized. A de novo crystal structure of the enzyme-substrate complex at 1.89-Å resolution provides the first comprehensive structural study of this hydroxylase. The binding conformation of l-tyrosine indicates that C-H bond hydroxylation is initiated by electron

SUBMITTER: Wang Y 

PROVIDER: S-EPMC8283942 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature