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Influence of human tryptophan hydroxylase 2 N- and Cterminus on enzymatic activity and oligomerization.

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons50622

Walther,  Diego J.
Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Tenner, K., Walther, D. J., & Bader, M. (2007). Influence of human tryptophan hydroxylase 2 N- and Cterminus on enzymatic activity and oligomerization. Journal of Neurochemistry: Official Journal of the International Society for Neurochemistry, 102(6), 1887-1894. doi:10.1111/j.1471-4159.2007.04664.x.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-8130-8
Abstract
Tryptophan hydroxylase (TPH) catalyses the first and rate limiting step in the biosynthesis of the neurotransmitter serotonin. There are two TPH isoenzymes in humans, encoded by two different genes: TPH1 and the recently described TPH2. We have expressed both human enzymes and various deletion mutants of TPH2 (ΔN44, ΔC17, ΔC19, ΔC51) in COS7 cells. TPH1 and 2 displayed different kinetic properties with a lower Km value of TPH1. Removal of 44 amino acids from the N-terminus of TPH2 resulted in a 3–4-fold increased Vmax, which indicates a strong inhibitory function of this part on the enzymes activity. TPH1 and 2 were able to form homooligomers and also heterooligomers with each other. The different deletion mutants (ΔC17, ΔC19 and ΔC51), which lack the putative C-terminal leucine zipper tetramerization domain, existed as monomeric enzymes. While short deletions (ΔC17 and ΔC19) hardly changed Vmax values, the ΔC51 mutant lost 99% of TPH activity. These data identify a region between the C-terminal oligomerization domain and the catalytic domain, which is indispensable for TPH2 activity.