title: Structural insights into the regulation of aromatic amino acid hydroxylation.
abstract: The aromatic amino acid hydroxylases phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase are homotetramers, with each subunit containing a homologous catalytic domain and a divergent regulatory domain. The solution structure of the regulatory domain of tyrosine hydroxylase establishes that it contains a core ACT domain similar to that in phenylalanine hydroxylase. The isolated regulatory domain of tyrosine hydroxylase forms a stable dimer, while that of phenylalanine hydroxylase undergoes a monomer-dimer equilibrium, with phenylalanine stabilizing the dimer. These solution properties are consistent with the regulatory mechanisms of the two enzymes, in that phenylalanine hydroxylase is activated by phenylalanine binding to an allosteric site, while tyrosine hydroxylase is regulated by binding of catecholamines in the active site.
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX 78229, United States. Electronic address: fitzpatrickp@uthscsa.edu.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Fitzpatrick
mesh_terms: D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D055503:Protein Multimerization
chemical_list: D024322:Amino Acids, Aromatic; D006899:Mixed Function Oxygenases