title: Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin.
abstract: Tryptophan hydroxylase oxidizes L-tryptophan to 5-hydroxy-L-tryptophan in the rate-determining step of serotonin biosynthesis. We have determined the X-ray crystal structure (1.7 A) of a truncated functional form of human tryptophan hydroxylase with the bound cofactor analogue 7,8-dihydro-L-biopterin, providing the first atomic-resolution information for the catalytic domain of this important enzyme. Comparison of the three-dimensional structures of all three members of the aromatic amino acid hydroxylase family--tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase--reveals important differences at the active sites.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Heidi
authors.initials: H
authors.lastname: Erlandsen
authors.forename: Jan
authors.initials: J
authors.lastname: Haavik
authors.forename: Per M
authors.initials: PM
authors.lastname: Knappskog
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Stevens
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D020134:Catalytic Domain / Q000235:genetics; D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D008550:Melatonin / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017384:Sequence Deletion; D012701:Serotonin / Q000096:biosynthesis*; D014365:Tryptophan Hydroxylase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D011994:Recombinant Proteins; D001708:Biopterins; D012701:Serotonin; C017226:7,8-dihydrobiopterin; D014365:Tryptophan Hydroxylase; D008550:Melatonin