PROBING THE SUBSTRATE SPECIFICITY OF ENDO-α-MANNOSIDASE WITH EPIMERIC α-MAN-1,3-α-MAN/α-GLC-1,3-α-MAN CONFIGURED SUBSTRATES AND INHIBITORS

摘要

Endo-α-mannosidase is an endo-acting GH99 glycosidase that provides an exo-glucosidase independent pathway for the biosynthesis of N-linked glycans. Endo-α-mannosidase relieves blockages in the biosynthesis of N-linked glycans should there be deficiencies or inhibition of exo-glucosidase activity. GH99 bacterial orthologs of endo-α-mannosidase including Bacteroides xylanisolvens (BxGH99) share the same substrate specificity, fold, key active-site residues and presumably mechanism with the mammalian enzyme. However, bacteria do not produce mammalian N-linked glycans, which raises questions regarding the role of bacterial endo-α-mannosidase. B. xylanisolvens is a common resident of the human gut and it has been suggested that in this environment they could encounter yeast mannans, which contain the epimeric α-mannosyl-1,3-mannose substructure of regular N-linked glycans. Endo-α-mannosidase may play a biologically-important role in the processing of high mannose glycans that would otherwise not be deglycosylated by exo-mannosidases.