Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin

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 Angstrom) 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.