XL-MS analysis of human tyrosine hydroxylase

Tyrosine hydroxylase (TH) is a highly regulated enzyme that catalyses the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines. Mutations and dysfunction in this enzyme lead to DA deficiency and parkinsonisms of different severity. An understanding of TH deficiency at the level of structure and stability has been lacking to date, as only structures of truncated TH forms have been available. Here, we used cryoEM and XL-MS to determine the high-resolution structure of full-length human tetrameric TH in the absence and presence of the end-product and feedback inhibitor DA bound to the active site