Hjem
Michael Sars-senteret

Varselmelding

There has not been added a translated version of this content. You can either try searching or go to the "area" home page to see if you can find the information there
GUEST SEMINARS AT THE MICHAEL SARS CENTRE

Prof. Aurora Martinez, UiB

Prof. Aurora Martinez, from the Department of Biomedicine at UiB, will present: "Regulatory mechanisms of dopamine synthesis: structural basis and pathogenic insights"

Hovedinnhold

Science image
Foto/ill.:
Aurora Martinez

Tyrosine hydroxylase (TH) is a member of the evolutionarily related tetrahydrobiopterin (BH4)-dependent aromatic amino acid hydroxylases. TH is the rate-limiting enzyme for dopamine (DA) biosynthesis, and its dysfunction leads to DA deficiency and parkinsonisms, a set of neurological disorders that cause motor impairment. Key regulatory mechanisms include inhibition by catecholamines, reactivation by S40 phosphorylation, and regulation by L-tyrosine and BH4 levels. Protein-protein interactions of TH with various regulatory proteins are also crucial. Cryo-EM studies reveal the mechanisms by which DA binding blocks the active site, while S40 phosphorylation reactivates it, maintaining DA and TH homeostasis. Additionally, the co-chaperone DNAJC12, along with the scaffold protein 14-3-3, are important for maintaining TH stability and regulated dopamine synthesis. Pathogenic variants in TH, as well as in DNAJC12 or 14-3-3, which may affect these protein interactions, lead to pediatric parkinsonisms. A structural understanding of these regulatory mechanisms and of the effects of pathogenic variants is essential for developing new therapies for parkinsonisms, as current treatments like L-Dopa are insufficient for severe cases. Biophysical and cellular screens have identified potential therapeutic compounds targeting these pathways.

Visit Prof. Martinez's website.