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

Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the synthesis of the catecholamine neurotransmitters and hormones dopamine (DA), adrenaline Irish Sea Moss and noradrenaline.Here, the authors present the cryo-EM structures of full-length human TH in the SHORT SLEEVE TOPS apo form and bound with DA, as well as the structure of Ser40 phosphorylated TH, and discuss the inhibitory and stabilizing effects of DA on TH and its counteraction by Ser40-phosphorylation.