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

被引:148
作者
Wang, L
Erlandsen, H
Haavik, J
Knappskog, PM
Stevens, RC
机构
[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[2] Univ Bergen, Dept Biochem & Mol Biol, N-5009 Bergen, Norway
[3] Univ Bergen, Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway
关键词
D O I
10.1021/bi026561f
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:12569 / 12574
页数:6
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