Human aromatic amino acid decarboxylase is an asymmetric and flexible enzyme: Implication in aromatic amino acid decarboxylase deficiency.

ABSTRACT: Human aromatic amino acid decarboxylase (AADC) is a pyridoxal 5'-phosphate-dependent enzyme responsible for the biosynthesis of dopamine and serotonin, essential neurotransmitters involved in motor and cognitive abilities. Mutations in its gene lead to AADC deficiency, a monogenic rare neurometabolic childhood parkinsonism characterized by severe motor and neurodevelopmental symptoms. Here, for the first time, we solved the crystal structure of human holoAADC in the internal aldimine (1.9 Å) and in the external aldimine (2.4 Å) of the substrate analog L-Dopa methylester. In this intermediate, the highly flexible AADC catalytic loop (CL) is captured in a closed state contacting all protein domains. In addition, each active site, composed by residues of both subunits, is connected to the oth

SUBMITTER: Bisello G 

PROVIDER: S-EPMC10382914 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature