title: Novel enhancement mechanism of tyrosine hydroxylase enzymatic activity by nitric oxide through S-nitrosylation.
abstract: Tyrosine hydroxylase (TH) is a rate-limiting step enzyme in the synthesis of catecholamines. Catecholamines function both as hormone and neurotransmitters in the peripheral and central nervous systems, therefore TH's expression and enzymatic activity is tightly regulated by various mechanisms. Several post-translational modifications have been shown to regulate TH's enzymatic activity such as phosphorylation, nitration and S-glutathionylation. While phosphorylation at N-terminal of TH can activate its enzymatic activity, nitration and S-glutathionylation can inactivate TH. In this study, we found that TH can also be S-nitrosylated by nitric oxide (NO). S-nitrosylation is a reversible modification of cysteine (cys) residue in protein and is known to be an emerging signaling mechanism mediated by NO. We found that TH can be S-nitrosylated at cys 279 and TH S-nitrosylation enhances its enzymatic activity both in vitro and in vivo. These results provide a novel mechanism of how NO can modulate TH's enzymatic activity through S-nitrosylation.
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Chun Chau
authors.initials: CC
authors.lastname: Sung
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Kenny K K
authors.initials: KK
authors.lastname: Chung
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D009569:Nitric Oxide; D014446:Tyrosine 3-Monooxygenase