ArticleNature communications2022
Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 82 citations in OpenAlex.
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- Impact of Ser81 phosphorylation on alanine: glyoxylate aminotransferase associated with Primary hyperoxaluria type I.Molecular biomedicine · 2026Article
- Tyrosine hydroxylase as a therapeutic target: insights from adrenergic nerve and TNBC cell interactions.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Tyrosine Hydroxylase Deficiency Impairs TH Axonal Transport, Brain Function, and Neuronal Plasticity.Journal of inherited metabolic disease · 2026Article
- Agonism of FFA4/GPR120 activates tyrosine hydroxylase and confers neuroprotection from 6-OHDA-induced cytotoxicity in PC12 cells and in a rat 6-OHDA model of Parkinson's disease.Biochemical pharmacology · 2026Article
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- Partitioned polygenic scores show mechanistic heterogeneity in type 2 diabetes and hypertension comorbidity.Nature communications · 2026Article
- Agaricus arvensis extract-coated functionalized silver nanoparticles for effective aerobic biotransformation of synthetic L-tyrosine to L-DOPA.AMB Express · 2026Article
- Combination antiviral and anti-inflammatory therapy mitigates persistent neurological deficits in mice post SARS-CoV-2 infection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multi-omics study of molecular and genetic bases of orthostatic hypotension.Clinical epigenetics · 2025Article
- Suppression of brain aromatase decreases the expression of dopaminergic neuron in early development of zebrafish.Fish physiology and biochemistry · 2025Article
- Retinal alterations resemble brain pathology in a rat model of Parkinson's disease induced by intranigral infusion of α-synuclein oligomers.Cell death discovery · 2025Article
- Paeonol Mitigates Neurodegeneration: Molecular Insights into Its Anti-inflammatory, Antioxidant, and Synaptoprotective Mechanisms.Molecular neurobiology · 2025Review
- Mechanistic Insight into Tyrosine Oxidation at Carbon-Fiber Microelectrodes Revealed by Fast-Scan Cyclic Voltammetry.ACS electrochemistry · 2025Article
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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 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.
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