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UDP-N-acetylglucosamine-dolichol phosphate N-acetylglucosaminephosphotransferase (DPAGT1)

Target: DPAGT1
Molecular classification: Enzyme, Glycosyltransferase

Overview

UDP-N-acetylglucosamine-dolichol phosphate N-acetylglucosaminephosphotransferase (DPAGT1/ALG7) is a membrane-bound enzyme that catalyzes the first committed step in the biosynthesis of dolichol-linked oligosaccharides, which are essential precursors for protein N-glycosylation in eukaryotes. Mutations in DPAGT1 lead to congenital disorders of glycosylation. As the enzyme catalyzes the initial step of LLO assembly, this step is required for N-glycosylation of proteins, a process critical for proper folding and function of many secretory and membrane proteins.

Other names: ALG7Dolichol-phosphate N-acetylglucosaminephosphotransferaseN-acetylglucosaminyl-diphosphodolichol synthase

Mechanism of action

Inhibitors would block the first committed step in LLO biosynthesis, thereby disrupting N-glycosylation.

Biological functions

Lipid-linked oligosaccharide (LLO) biosynthesisN-glycosylationProtein foldingER quality control

Disease associations

Congenital disorders of glycosylation type Ij (DPAGT1-CDG)Limb-girdle congenital myasthenic syndrome with tubular aggregates

Safety considerations

Inhibition of this enzyme can lead to severe defects in glycoprotein synthesis and potentially cell death, due to the critical role of N-glycosylation. Global inhibition is likely lethal.Targeting the enzyme specifically in disease settings like cancer may be feasible but requires careful consideration of off-target effects.

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