title: A unique dual activity amino acid hydroxylase in Toxoplasma gondii.
abstract: The genome of the protozoan parasite Toxoplasma gondii was found to contain two genes encoding tyrosine hydroxylase; that produces L-DOPA. The encoded enzymes metabolize phenylalanine as well as tyrosine with substrate preference for tyrosine. Thus the enzymes catabolize phenylalanine to tyrosine and tyrosine to L-DOPA. The catalytic domain descriptive of this class of enzymes is conserved with the parasite enzyme and exhibits similar kinetic properties to metazoan tyrosine hydroxylases, but contains a unique N-terminal extension with a signal sequence motif. One of the genes, TgAaaH1, is constitutively expressed while the other gene, TgAaaH2, is induced during formation of the bradyzoites of the cyst stages of the life cycle. This is the first description of an aromatic amino acid hydroxylase in an apicomplexan parasite. Extensive searching of apicomplexan genome sequences revealed an ortholog in Neospora caninum but not in Eimeria, Cryptosporidium, Theileria, or Plasmodium. Possible role(s) of these bi-functional enzymes during host infection are discussed.
authors.affiliation: Institute of Integrative and Comparative Biology, University of Leeds, Leeds, United Kingdom.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Gaskell
authors.forename: Judith E
authors.initials: JE
authors.lastname: Smith
authors.forename: John W
authors.initials: JW
authors.lastname: Pinney
authors.forename: Dave R
authors.initials: DR
authors.lastname: Westhead
authors.forename: Glenn A
authors.initials: GA
authors.lastname: McConkey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D005347:Fibroblasts / Q000469:parasitology; D018507:Gene Expression Regulation, Developmental; D017125:Genes, Protozoan; D006801:Humans; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000378:metabolism; D010651:Phenylalanine Hydroxylase / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D011622:Pterins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D016053:RNA, Protozoan / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013379:Substrate Specificity; D014122:Toxoplasma / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D014443:Tyrosine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D011622:Pterins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D010649:Phenylalanine; C017523:6-methyltetrahydropterin; D010651:Phenylalanine Hydroxylase; D014446:Tyrosine 3-Monooxygenase