PROSITE documentation PDOC00316

Biopterin-dependent aromatic amino-acid hydroxylases [1] are iron-dependent enzymes that catalyze a mixed oxidation reaction. This consumes a reduced biopterin cofactor and molecular oxygen for the hydroxylation of an aromatic amino-acid substrate. Enzymes that belong to this family, and for which sequence data is available, are listed below.

Phenylalanine-4-hydroxylase (EC 1.14.16.1) (PAH). Catalyzes the conversion of phenylalanine to tyrosine. In humans, deficiencies [2,E1] of PAH are the cause of phenylketonuria, the most common inborn error of amino acid metabolism. In the bacteria Chromobacterium violaceum [3], PAH is copper- dependent; it is iron-dependent in Pseudomonas aeruginosa [4].
Tyrosine 3-hydroxylase (EC 1.14.16.2) (TYH). Catalyzes the rate limiting step in catecholamine biosynthesis: the conversion of tyrosine to 3,4- dihydroxy-L-phenylalanine.
Tryptophan 5-hydroxylase (EC 1.14.16.4) (TRH). Catalyzes the rate-limiting step in serotonin biosynthesis: the conversion of tryptophan to 3-hydroxy- anthranilate.

Enzymes that belong to this family are functionally as well as structurally related [2]. Their size ranges from 260 residues for bacterial PAH, to about 500 residues for eukaryotic PAH, TYH and TRH. As a signature pattern for this family, we selected a conserved region in the central part of these enzymes, which contains two conserved histidines that are involved in the binding to iron or copper [5].

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1	Authors	Grenett H.E., Ledley F.D., Reed L.L., Woo S.L.C.
	Title	Full-length cDNA for rabbit tryptophan hydroxylase: functional domains and evolution of aromatic amino acid hydroxylases.
	Source	Proc. Natl. Acad. Sci. U.S.A. 84:5530-5534(1987).
	PubMed ID	3475690

2	Authors	Hoang L., Byck S., Prevost L., Scriver C.R.
	Title	PAH Mutation Analysis Consortium Database: a database for disease-producing and other allelic variation at the human PAH locus.
	Source	Nucleic Acids Res. 24:127-131(1996).
	PubMed ID	8594560

3	Authors	Onishi A., Liotta L.J., Benkovic S.J.
	Title	Cloning and expression of Chromobacterium violaceum phenylalanine hydroxylase in Escherichia coli and comparison of amino acid sequence with mammalian aromatic amino acid hydroxylases.
	Source	J. Biol. Chem. 266:18454-18459(1991).
	PubMed ID	1655752

4	Authors	Zhao G.S., Xia T., Song J., Jensen R.A.
	Title	Pseudomonas aeruginosa possesses homologues of mammalian phenylalanine hydroxylase and 4 alpha-carbinolamine dehydratase/DCoH as part of a three-component gene cluster.
	Source	Proc. Natl. Acad. Sci. U.S.A. 91:1366-1370(1994).
	PubMed ID	8108417

5	Authors	Goodwill K.E., Sabatier C., Marks C., Raag R., Fitzpatrick P.F., Stevens R.C.
	Title	Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases.
	Source	Nat. Struct. Biol. 4:578-585(1997).
	PubMed ID	9228951

Biopterin-dependent aromatic amino acid hydroxylases signature

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