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 Å) 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 familytyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylasereveals important differences at the active sites.