Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation.
Journal, issue, pages	Nat Commun, Vol. 13, Issue 1, Page 74, Year 2022
Publish date	Jan 10, 2022
Authors	María Teresa Bueno-Carrasco / Jorge Cuéllar / Marte I Flydal / César Santiago / Trond-André Kråkenes / Rune Kleppe / José R López-Blanco / Miguel Marcilla / Knut Teigen / Sara Alvira / Pablo Chacón / Aurora Martinez / José M Valpuesta /
PubMed Abstract	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 ...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 biochemical characterizations and molecular dynamics simulations. TH presents a tetrameric structure with dimerized regulatory domains that are separated 15 Å from the catalytic domains. Upon DA binding, a 20-residue α-helix in the flexible N-terminal tail of the regulatory domain is fixed in the active site, blocking it, while S40-phosphorylation forces its egress. The structures reveal the molecular basis of the inhibitory and stabilizing effects of DA and its counteraction by S40-phosphorylation, key regulatory mechanisms for homeostasis of DA and TH.
External links	Nat Commun / PubMed:35013193 / PubMed Central
Methods	EM (single particle)
Resolution	3.5 - 4.6 Å
Structure data	11309 6zn2 EMDB-11309, PDB-6zn2: Partial structure of tyrosine hydroxylase in complex with dopamine showing the catalytic domain and an alpha-helix from the regulatory domain involved in dopamine binding. Method: EM (single particle) / Resolution: 4.3 Å 11467 6zvp EMDB-11467, PDB-6zvp: Atomic model of the EM-based structure of the full-length tyrosine hydroxylase in complex with dopamine (residues 40-497) in which the regulatory domain (residues 40-165) has been included only with the backbone atoms Method: EM (single particle) / Resolution: 4.0 Å 11587 6zzu EMDB-11587, PDB-6zzu: Partial structure of the substrate-free tyrosine hydroxylase (apo-TH). Method: EM (single particle) / Resolution: 3.5 Å 11624 7a2g EMDB-11624, PDB-7a2g: Full-length structure of the substrate-free tyrosine hydroxylase (apo-TH). Method: EM (single particle) / Resolution: 4.1 Å EMDB-13177: Ser40 phosphorylated tyrosine hydroxylase Method: EM (single particle) / Resolution: 4.5 Å 13442 7pim EMDB-13442, PDB-7pim: Partial structure of tyrosine hydroxylase lacking the first 35 residues in complex with dopamine. Method: EM (single particle) / Resolution: 4.6 Å
Chemicals	ChemComp-LDP: L-DOPAMINE / medicationYM / Dopamine (medication) ChemComp-FE: Unknown entry / Iron ChemComp-HOH*: WATER / Water
Source	homo sapiens (human)
Keywords	OXIDOREDUCTASE / Tetramer / Dopamine / Catecholamine / Brain / Parkinson