Structure, Function and Mechanism of N-Glycan Processing Enzymes: endo-alpha-1,2-Mannanase and endo-alpha-1,2-Mannosidase

Abstract

While most glycosidases that act on N-linked glycans remove a single sugar residue at a time, endo-α-1,2-mannosidases and endo-α-1,2-mannanases of glycoside hydrolase family GH99 cut within a chain and remove two or more sugar residues. They are stereochemically retaining enzymes that use an enzymatic mechanism involving an epoxide intermediate. Human endo-α-1,2-mannosidase (MANEA) trims glucosylated mannose residues; the endomannosidase pathway provides a glucosidase-independent pathway for glycoprotein maturation. Cell-active MANEA inhibitors alter N-glycan processing and reduce infectivity of dengue virus, demonstrating that MANEA has potential as a host-directed antiviral target. Sequenc..