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

• Published in: Nature communications Vol. 13; no. 1; p. 74
• Main Authors: Bueno-Carrasco, María Teresa, Cuéllar, Jorge, Flydal, Marte I., Santiago, César, Kråkenes, Trond-André, Kleppe, Rune, López-Blanco, José R., Marcilla, Miguel, Teigen, Knut, Alvira, Sara, Chacón, Pablo, Martinez, Aurora, Valpuesta, José M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.01.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 101/58; 631/378/340; 631/535/1258/1259; 82/16; 82/80; 82/83; Amino Acid Sequence; Biosynthesis; Catalytic Domain; Catecholamine; Catecholamines; Catecholamines - metabolism; Constraining; Cryoelectron Microscopy; Domains; Dopamine; Dopamine - chemistry; Dopamine - metabolism; Dopamine - pharmacology; Egress; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Epinephrine; Homeostasis; Hormones; Humanities and Social Sciences; Humans; Hydroxylase; Models, Molecular; Molecular dynamics; multidisciplinary; Neurotransmitters; Noradrenaline; Norepinephrine; Phosphorylation; Protein Binding; Protein Domains; Regulatory mechanisms (biology); Science; Science (multidisciplinary); Tyrosine; Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - antagonists & inhibitors; Tyrosine 3-Monooxygenase - chemistry; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism

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 an...