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PCSK9 interacts with LDL receptor, causing its degradation, and consequently reduces the clearance of LDL. Here, Gustafsen et al. show that PCSK9 interacts with heparan sulfate proteoglycans and this binding favors LDLR degradation. Pharmacological inhibition of this binding can be exploited as therapeutic intervention to lower LDL levels.
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.