page_title: Tyrosine hydroxylase
section_title: Structure
hierarchical_section_title: Tyrosine hydroxylase / Structure
caption_attribution_description: English: This image shows tyrosine hydroxylase's tetramerization (pink) and catalyzation (blue) domains.
context_page_description: Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine. It does so using molecular oxygen, as well as iron and tetrahydrobiopterin as cofactors. L-DOPA is a precursor for dopamine, which, in turn, is a precursor for the important neurotransmitters norepinephrine and epinephrine. Tyrosine hydroxylase catalyzes the rate limiting step in this synthesis of catecholamines. In humans, tyrosine hydroxylase is encoded by the TH gene, and the enzyme is present in the central nervous system, peripheral sympathetic neurons and the adrenal medulla. Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase together make up the family of aromatic amino acid hydroxylases.
context_section_description: Tyrosine hydroxylase is a tetramer of four identical subunits (homotetramer). Each subunit consists of three domains. At the carboxyl terminal of the peptide chain there's a short alpha helix domain that allows tetramerization. The central ~300 amino acids make up a catalytic core, in which all the residues necessary for catalysis are located, along with a non-covalently bound iron atom. The iron is held in place by two histidine residues and one glutamate residue, making it a non-heme, non-iron-sulfur iron-containing enzyme. The amino terminal ~150 amino acids make up a regulatory domain, thought to control access of substrates to the active site. In humans there are thought to be four different versions of this regulatory domain, and thus four versions of the enzyme, depending on alternative splicing, though none of their structures have yet been properly determined. It has been suggested that this domain might be an intrinsically unstructured protein, which has no clearly defined tertiary structure, but so far no evidence has been presented supporting this claim. It has however been shown that the domain has a low occurrence of secondary structures, which doesn't weaken suspicions of it having a disordered overall structure. As for the tetramerization and catalytic domains their structure was found with rat tyrosine hydroxylase using X-ray crystallography. This has shown how its structure is very similar to that of phenylalanine hydroxylase and tryptophan hydroxylase; together the three make up a family of homologous aromatic amino acid hydroxylases.
caption: Tyrosine hydroxylase from rat showing two of its domains, the tetramerization domain (pink) and the catalytic domain (blue). The regulatory domain (not shown) would sit somewhere on the right hand side of the image where also the enzyme's substrate would enter from.
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