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O-GlcNAc is a reversible post-translational modification that is added by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). OGA is emerging as a therapeutic target for multiple diseases, but its structure has been elusive until now.
Proteolytic maturation of an important transcriptional regulator is performed by a glycosyltransferase. The reaction involves glycosylation of a glutamate residue and conversion of the γ-glycosyl ester product into an N-acyl pyroglutamate, which undergoes spontaneous hydrolysis to effect peptide backbone fission.
Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat bacterial infections.