Biopterin-dependent aromatic amino acid hydroxylase
crystal structure of ternary complex of the catalytic domain of human phenylalanine hydroxylase (Fe(II)) complexed with tetrahydrobiopterin and norleucine
In molecular biology, the biopterin-dependent aromatic amino acid hydroxylases (abbreviated AAAH) constitute a family of aromatic amino acid hydroxylases, including phenylalanine 4-hydroxylase (EC 22.214.171.124), tyrosine 3-hydroxylase (EC 126.96.36.199), and tryptophan 5-hydroxylase (EC 188.8.131.52). These enzymes primarily hydroxylate phenylalanine, tyrosine, and tryptophan, respectively. These enzymes are all rate-limiting catalysts for important metabolic pathways. The proteins are structurally and functionally related, each containing iron, and catalysing ring hydroxylation of aromatic amino acids, using tetrahydrobiopterin (BH4) as a substrate. All are regulated by phosphorylation at serines in their N-termini. It has been suggested that the proteins each contain a conserved C-terminal catalytic (C) domain and an unrelated N-terminal regulatory (R) domain. It is possible that the R domains arose from genes that were recruited from different sources to combine with the common gene for the catalytic core. Thus, by combining with the same C domain, the proteins acquired the unique regulatory properties of the separate R domains.
In humans, phenylalanine hydroxylase deficiency can cause of phenylketonuria, the most common inborn error of amino acid metabolism, Tryptophan hydroxylase catalyzes the rate-limiting step in serotonin biosynthesis: the conversion of tryptophan to 5-hydroxy-L-tryptophan and tyrosine hydroxylase catalyzes the rate limiting step in catecholamine biosynthesis: the conversion of tyrosine to L-DOPA.
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