Hydroxylation of the aromatic amino acids phenylalanine, tyrosine and
tryptophan is carried out by a family of non-heme iron and tetrahydrobiopterin
(BH4) dependent enzymes: the aromatic amino acid hydroxylase . These
enzymes are structurally and functionally similar. The eukaryotic forms
include a regulatory N-terminal domain, a catalytic domain and a C-terminal
oligomerization motif. The eukaryotic enzymes are all homotetramers [2,3].
Three-dimensional structures have been determined for the three types of
enzymes (see for example <PDB:1J8U>). The iron atom is bound to three amino
acid residues, two close histidine and a more distant acidic residue. This
arrangement of ligands has been observed in a number of metalloproteins with
divergent function .
Enzymes that belong to the aromatic amino acid hydroxylase family are listed
Phenylalanine-4-hydroxylase (EC 184.108.40.206) (PAH). Catalyzes the conversion
of phenylalanine to tyrosine. In humans, deficiencies  of PAH are the
cause of phenylketonuria, the most common inborn error of amino acid
metabolism. In the bacteria Chromobacterium violaceum , PAH is copper-
dependent; it is iron-dependent in Pseudomonas aeruginosa .
Tyrosine 3-hydroxylase (EC 220.127.116.11) (TYH). Catalyzes the rate limiting
step in catecholamine biosynthesis: the conversion of tyrosine to 3,4-
Tryptophan 5-hydroxylase (EC 18.104.22.168) (TRH). Catalyzes the rate-limiting
step in serotonin biosynthesis: the conversion of tryptophan to 3-hydroxy-
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. The profile we developed contains the
catalytic domain and the coiled-coil C-terminal oligomerization motif.
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