Mucin-related glycosidases and glycosyltransferases

Mucin-related glycosidases and glycosyltransferases represent a broad functional class of enzymes that orchestrate the complex post-translational modification of mucin proteins through O-glycosylation. Glycosyltransferases, such as the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, initiate the synthesis of O-glycan chains by attaching N-acetylgalactosamine to serine or threonine residues, while subsequent enzymes elongate these chains to form diverse structures like the Core 1 and Core 2 glycans (Brockhausen et al., 2022). Conversely, glycosidases such as sialidases (neuraminidases) and O-glycanases are responsible for the catabolism and remodeling of these glycans, a process essential for mucus turnover and cellular signaling (Tailford et al., 2015). Dysregulation of these enzymes is a hallmark of various pathologies; for instance, the overexpression of specific glycosyltransferases in cancer leads to the production of truncated glycans like the Tn and Sialyl-Tn antigens, which facilitate tumor invasion and immune evasion (Pinho & Reis, 2015). Therapeutic strategies targeting these enzymes aim to restore normal glycosylation patterns or inhibit the degradation of the protective mucus layer in inflammatory conditions. While several small-molecule inhibitors are used as research tools, clinical development is primarily focused on specific isoforms involved in oncology and metabolic disorders (Bennett et al., 2012).

Other names

Mucin O-glycosylation enzymesO-glycan processing enzymesMucin-type O-glycan glycosyltransferases and glycosidasesPolypeptide N-acetylgalactosaminyltransferases and sialidases

Inhibition of glycosyltransferase activity to prevent glycan chain elongation or inhibition of glycoside hydrolases to prevent the cleavage of terminal sugar residues such as sialic acid.