Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation

@article{BuenoCarrasco2022StructuralMF,
  title={Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation},
  author={M. Teresa Bueno-Carrasco and Jorge Cu{\'e}llar and Marte Innselset Flydal and C{\'e}sar Santiago and Trond-Andr{\'e} Kr{\aa}kenes and Rune Kleppe and Jos{\'e} Ram{\'o}n L{\'o}pez-Blanco and Miguel Marcilla and Knut Erik Teigen and Sara Alvira and Pablo Chac{\'o}n and Aurora Mart{\'i}nez and Jos{\'e} Mar{\'i}a Valpuesta},
  journal={Nature Communications},
  year={2022},
  volume={13}
}
Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines, and its dysfunction leads to DA deficiency and parkinsonisms. Inhibition by catecholamines and reactivation by S40 phosphorylation are key regulatory mechanisms of TH activity and conformational stability. We used Cryo-EM to determine the structures of full-length human TH without and with DA, and the structure of S40 phosphorylated TH, complemented with biophysical and… 
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