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Mannosyl-oligosaccharide 1,2-alpha-mannosidase IA (MAN1A1) is a Golgi-resident enzyme involved in the maturation of Asn-linked (N-linked) oligosaccharides during protein glycosylation. Specifically, MAN1A1 is one of three human Golgi alpha-1,2-mannosidases (along with MAN1A2 and MAN1C1), which trim mannose residues from Man9GlcNAc2 to produce Man5GlcNAc2, a critical step for the formation of complex N-glycans[1][4]. This process is required for proper protein folding, quality control, and trafficking of glycoproteins. The regulation and activity of MAN1A1 affect cell growth, cell–cell adhesion, motility, and protein degradation pathways[1]. Inhibition of this enzyme disrupts these processes, which has implications for cancer cell proliferation and is being investigated as a potential therapeutic strategy[6]. MAN1A1 belongs to glycoside hydrolase family 47 and, like other members of this family, adopts a (α/α)7 barrel fold, using a coordinated Ca2+ ion in its active site for catalysis[3].
Competitive inhibition of the enzymatic active site, blocking mannose residue trimming from glycoproteins
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