Fiebig T, Cramer JT, Bethe A, Baruch P, Curth U, Fuhring JI, Buettner FFR, Vogel U, Schubert M, Fedorov R, Muhlenhoff M Structural and mechanistic basis of capsule O-acetylation in Neisseria meningitidis serogroup A Nature Communications11(1) (2020)
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-6)-a-D-ManpNAc-(1-P-
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Ac-4)-
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Ac-3)-
NCBI PubMed ID:32948778 Publication DOI:10.1038/s41467-020-18464-y Journal NLM ID:101528555 Publisher: London: Nature Publishing Group Correspondence: Fiebig.Timmmh-hannover.de; Muehlenhoff.Martinamh-hannover.de Institutions: Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany, Institute for Virology, Hannover Medical School, Hannover, Germany, Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany, Fraunhofer International Consortium for Anti-Infective Research (iCAIR), Hannover, Germany, Institute for Hygiene and Microbiology, University of Wurzburg, Wurzburg, Germany, Department of Biosciences, University of Salzburg, Salzburg, Austria
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 alpha/beta-hydrolase fold.
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