6YUS

Capsule O-acetyltransferase of Neisseria meningitidis serogroup A H228A mutant in complex with CoA

Summary for 6YUS

• Entry DOI: 10.2210/pdb6yus/pdb
• Descriptor: SacC, COENZYME A, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• Functional Keywords: o-acetyltransferase, a/b hydrolase fold, serine transferase, catalytic triad, transferase
• Biological source: Neisseria meningitidis serogroup A
• Total number of polymer chains: 2
• Total formula weight: 60508.19

Authors

Cramer, J.T.,Fiebig, T.,Fedorov, R.,Muehlenhoff, M. (deposition date: 2020-04-27, release date: 2020-08-19, Last modification date: 2024-10-23)

Primary citation

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.
Structural and mechanistic basis of capsule O-acetylation in Neisseria meningitidis serogroup A.
Nat Commun, 11:4723-4723, 2020

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.

PubMed: 32948778
DOI: 10.1038/s41467-020-18464-y

Experimental method

X-RAY DIFFRACTION (2 Å)