Structural and mechanistic basis of capsule O-acetylation in Neisseria meningitidis serogroup A

Nat Commun. 2020 Sep 18;11(1):4723. doi: 10.1038/s41467-020-18464-y.


O-Acetylation of the capsular polysaccharide (CPS) of Neisseria meningitidis serogroup A (NmA) is critical for the induction of functional immune responses, making this modification mandatory for CPS-based anti-NmA vaccines. Using comprehensive NMR studies, we demonstrate that O-acetylation stabilizes the labile anomeric phosphodiester-linkages of the NmA-CPS and occurs in position C3 and C4 of the N-acetylmannosamine units due to enzymatic transfer and non-enzymatic ester migration, respectively. To shed light on the enzymatic transfer mechanism, we solved the crystal structure of the capsule O-acetyltransferase CsaC in its apo and acceptor-bound form and of the CsaC-H228A mutant as trapped acetyl-enzyme adduct in complex with CoA. Together with the results of a comprehensive mutagenesis study, the reported structures explain the strict regioselectivity of CsaC and provide insight into the catalytic mechanism, which relies on an unexpected Gln-extension of a classical Ser-His-Asp triad, embedded in an α/β-hydrolase fold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetyltransferases
  • Antibodies, Bacterial
  • Bacterial Capsules / chemistry*
  • Bacterial Capsules / genetics
  • Bacterial Capsules / immunology
  • Bacterial Capsules / metabolism*
  • Bacterial Vaccines / immunology
  • Hexosamines
  • Models, Molecular
  • Neisseria meningitidis, Serogroup A / genetics
  • Neisseria meningitidis, Serogroup A / metabolism*
  • Polysaccharides, Bacterial / chemistry*
  • Polysaccharides, Bacterial / genetics
  • Polysaccharides, Bacterial / immunology
  • Polysaccharides, Bacterial / metabolism*
  • Protein Conformation


  • Antibodies, Bacterial
  • Bacterial Vaccines
  • Hexosamines
  • Polysaccharides, Bacterial
  • Acetyltransferases
  • N-acetylmannosamine