Dataset Information

XL-MS analysis of human tyrosine hydroxylase

ABSTRACT: 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

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Miguel Marcilla

LAB HEAD: Fernando Corrales

PROVIDER: PXD024519 | Pride | 2021-12-22

REPOSITORIES: Pride

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

Bueno-Carrasco María Teresa MT Cuéllar Jorge J Flydal Marte I MI Santiago César C Kråkenes Trond-André TA Kleppe Rune R López-Blanco José R JR Marcilla Miguel M Teigen Knut K Alvira Sara S Chacón Pablo P Martinez Aurora A Valpuesta José M JM

Nature communications 20220110 1

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 bioch ...[more]

PMID: 35013193

Publication: 1/2

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			Action	DRS
	TB05_M1.csv	Csv
	TB05_M1.mgf	Mgf
	TB05_M1.wiff	Wiff
	TB05_M1.wiff.scan	Wiff
	TB05_M2.csv	Csv