Download MendeleyStructural and mechanistic basis of capsule O-acetylation in Neisseria meningitidis serogroup A.
Fiebig, T., Cramer, J.T., Bethe, A., Baruch, P., Curth, U., Fuhring, J.I., Buettner, F.F.R., Vogel, U., Schubert, M., Fedorov, R., Muhlenhoff, M.(2020) Nat Commun 11: 4723-4723
- PubMed: 32948778
- DOI: https://doi.org/10.1038/s41467-020-18464-y
- Primary Citation of Related Structures:
6YUO, 6YUQ, 6YUS, 6YUV - PubMed Abstract:
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.
Organizational Affiliation:
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany. [email protected].
