Phenylalanine hydroxylase
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Phenylalanine hydroxylase (eg. EC 1.14.16.1 (http://www.expasy.org/cgi-bin/nicezyme.pl?1.14.16.1)) is an enzyme which catalyses the reaction causing the addition of an hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine. Phenylalanine hydroxylase is the rate-limiting enzyme of the metabolic pathway which degrades excess phenylalanine. Mutations in phenylalanine hydroxylase which result in lower activity are the cause of the disease phenylketonuria, or PKU. The other substrates in the reaction are molecular oxygen and tetrahydrobiopterin. Tetrahydrobiopterin is a member of the group of redox biochemicals known as pteridines.
Phenylalanine hydroxylase is a tetramer, that is, composed of four subunits. Each subunit is in turn composed of three domains, a regulatory domain, a catalytic domain, and a tetramerization domain. The regulatory domain is composed of the approximately 115 amino acids nearest the amino terminal of the subunit. The catalytic domain is composed of the next approximately 300 amino acids, and is responsible for all of the catalytic activity of the enzyme. The tetramerization domain consists of the remaining amino acids and through the formation of a "coiled-coil" arrangement of amino acids, holds the tetrameric structure of the holoenzyme together with a "leucine zipper". Phenylalanine hydroxylase contains one bound iron atom per subunit which is necessary for catalytic activity.