IPR001273
Aromatic amino acid hydroxylase
InterPro entry
Short name | ArAA_hydroxylase |
Overlapping homologous superfamilies | |
family relationships |
Description
Phenylalanine, tyrosine and tryptophan hydroxylases constitute a family of tetrahydrobiopterin-dependent aromatic amino acid hydroxylases, all of which are rate-limiting catalysts for important metabolic pathways
[1]. The proteins are structurally and functionally related, each containing iron, and catalysing ring hydroxylation of aromatic amino acids, using tetra-hydrobiopterin (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.
A variety of enzymes belong to this family that includes, phenylalanine-4-hydroxylase from Chromobacterium violaceum where it is copper-dependent; it is iron-dependent in Pseudomonas aeruginosa, phenylalanine-4-hydroxylase catalyzes the conversion of phenylalanine to tyrosine. In humans, deficiencies are the cause of phenylketonuria, the most common inborn error of amino acid metabolism
[2], tryptophan 5-hydroxylase catalyzes the rate-limiting step in serotonin biosynthesis: the conversion of tryptophan to 3-hydroxy-anthranilate and tyrosine 3-hydroxylase catalyzes the rate limiting step in catecholamine biosynthesis: the conversion of tyrosine to 3,4-dihydroxy-L-phenylalanine.
References
1.Full-length cDNA for rabbit tryptophan hydroxylase: functional domains and evolution of aromatic amino acid hydroxylases. Grenett HE, Ledley FD, Reed LL, Woo SL. Proc. Natl. Acad. Sci. U.S.A. 84, 5530-4, (1987). View articlePMID: 3475690
2.Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria. Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC. Nat. Struct. Biol. 4, 995-1000, (1997). View articlePMID: 9406548
GO terms
biological process
molecular function
cellular component
- None
Cross References
Contributing Member Database Entry
- PANTHER:PTHR11473