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 [1]. 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 [4].

Enzymes that belong to the aromatic amino acid hydroxylase family are listed below:

• Phenylalanine-4-hydroxylase (EC 1.14.16.1) (PAH). Catalyzes the conversion of phenylalanine to tyrosine. In humans, deficiencies [5,E1] of PAH are the cause of phenylketonuria, the most common inborn error of amino acid metabolism. In the bacteria Chromobacterium violaceum [6], PAH is copper- dependent; it is iron-dependent in Pseudomonas aeruginosa [7].
• 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.

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.