Structures of ALG3/9/12 reveal the assembly logic of the N-glycan oligomannose core - PubMed
a day ago
- #enzyme structures
- #glycosylation
- #congenital disorders
- Structures of ALG3/9/12 enzymes reveal how the N-glycan oligomannose core is assembled.
- The biosynthesis involves dolichylpyrophosphate-anchored GlcNAc2Man9Glc3 glycan and over a dozen membrane proteins, with dysfunction linked to congenital disorders of glycosylation (CDGs).
- ALG3, ALG9, and ALG12 perform four mannosylation reactions converting GlcNAc2Man5 to GlcNAc2Man9.
- High-resolution cryo-EM structures of pseudo-Michaelis complexes show how branched glycans are synthesized accurately.
- Molecular dynamics and mutagenesis studies explain substrate selection over dolichylphosphoglucose.
- Findings provide insights into CDG enzyme dysfunction and potential for N-glycan engineering.