Influence of human tryptophan hydroxylase 2 N- and C-terminus on enzymatic activity and oligomerization

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Item Type:	Article
Title:	Influence of human tryptophan hydroxylase 2 N- and C-terminus on enzymatic activity and oligomerization
Creators Name:	Tenner, K., Walther, D. and Bader, M.
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 (DeltaN44, DeltaC17, DeltaC19, DeltaC51) in COS7 cells. TPH1 and 2 displayed different kinetic properties with a lower K(m) value of TPH1. Removal of 44 amino acids from the N-terminus of TPH2 resulted in a 3-4-fold increased V(max), 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 (DeltaC17, DeltaC19 and DeltaC51), which lack the putative C-terminal leucine zipper tetramerization domain, existed as monomeric enzymes. While short deletions (DeltaC17 and DeltaC19) hardly changed V(max) values, the DeltaC51 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.
Keywords:	Deletion Mutants, Domain Structure, Oligomerization, Serotonin, Tryptophan Hydroxylase 2, Animals
Source:	Journal of Neurochemistry
ISSN:	0022-3042
Publisher:	Blackwell Publishing
Volume:	102
Number:	6
Page Range:	1887-1894
Date:	September 2007
Official Publication:	https://doi.org/10.1111/j.1471-4159.2007.04664.x
PubMed:	View item in PubMed

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