The polysialic acid-specific O-acetyltransferase OatC from Neisseria meningitidis serogroup C evolved apart from other bacterial sialate O-acetyltransferases

J Biol Chem. 2009 Jan 2;284(1):6-16. doi: 10.1074/jbc.M807518200. Epub 2008 Nov 5.

Abstract

Neisseria meningitidis serogroup C is a major cause of bacterial meningitis and septicaemia. This human pathogen is protected by a capsule composed of alpha2,9-linked polysialic acid that represents an important virulence factor. In the majority of strains, the capsular polysaccharide is modified by O-acetylation at C-7 or C-8 of the sialic acid residues. The gene encoding the capsule modifying O-acetyltransferase is part of the capsule gene complex and shares no sequence similarities with other proteins. Here, we describe the purification and biochemical characterization of recombinant OatC. The enzyme was found as a homodimer, with the first 34 amino acids forming an efficient oligomerization domain that worked even in a different protein context. Using acetyl-CoA as donor substrate, OatC transferred acetyl groups exclusively onto polysialic acid joined by alpha2,9-linkages and did not act on free or CMP-activated sialic acid. Motif scanning revealed a nucleophile elbow motif (GXS286XGG), which is a hallmark of alpha/beta-hydrolase fold enzymes. In a comprehensive site-directed mutagenesis study, we identified a catalytic triad composed of Ser-286, Asp-376, and His-399. Consistent with a double-displacement mechanism common to alpha/beta-hydrolase fold enzymes, a covalent acetylenzyme intermediate was found. Together with secondary structure prediction highlighting an alpha/beta-hydrolase fold topology, our data provide strong evidence that OatC belongs to the alpha/beta-hydrolase fold family. This clearly distinguishes OatC from all other bacterial sialate O-acetyltransferases known so far because these are members of the hexapeptide repeat family, a class of acyltransferases that adopt a left-handed beta-helix fold and assemble into catalytic trimers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl Coenzyme A / chemistry*
  • Acetyl Coenzyme A / genetics
  • Acetyl Coenzyme A / metabolism
  • Acetyltransferases / chemistry*
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Amino Acid Motifs / physiology
  • Bacterial Capsules / chemistry
  • Bacterial Capsules / genetics
  • Bacterial Capsules / metabolism
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Evolution, Molecular*
  • Humans
  • N-Acetylneuraminic Acid / biosynthesis
  • N-Acetylneuraminic Acid / chemistry*
  • N-Acetylneuraminic Acid / metabolism
  • Neisseria meningitidis, Serogroup C / enzymology*
  • Neisseria meningitidis, Serogroup C / genetics
  • Protein Folding
  • Protein Structure, Quaternary / physiology
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics

Substances

  • Bacterial Proteins
  • Recombinant Proteins
  • Acetyl Coenzyme A
  • Acetyltransferases
  • N-acylneuraminate-9(7)-O-acetyltransferase
  • N-Acetylneuraminic Acid