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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites / genetics
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Biopterins / analogs & derivatives*
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Biopterins / metabolism
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Catalytic Domain / genetics
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Crystallography, X-Ray
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Humans
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Kinetics
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Melatonin / biosynthesis*
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Molecular Sequence Data
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Neurotransmitter Agents / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Alignment
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Sequence Deletion
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Serotonin / biosynthesis*
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Tryptophan Hydroxylase / chemistry*
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Tryptophan Hydroxylase / genetics
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Tryptophan Hydroxylase / metabolism*
Substances
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Neurotransmitter Agents
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Recombinant Proteins
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Biopterins
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Serotonin
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7,8-dihydrobiopterin
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Tryptophan Hydroxylase
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Melatonin