Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: meningitis [ICD11:
1D01 
];
septicemia [ICD11:
MA15.Y ];
infection due to Neisseria meningitidis [ICD11:
XN1DV ]
NCBI PubMed ID: 18986988Publication DOI: 10.1074/jbc.M807518200Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: muehlenhoff.martina
mh-hannover.de
Institutions: Department of Cellular Chemistry, Medical School Hannover, 30623 Hannover, Germany
Neisseria meningitidis serogroup C is a major cause of bacterial meningitis and septicaemia. This human pathogen is protected by a capsule composed of α2,9-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 α2,9-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 α/β-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 α/β-hydrolase fold enzymes, a covalent acetylenzyme intermediate was found. Together with secondary structure prediction highlighting an α/β-hydrolase fold topology, our data provide strong evidence that OatC belongs to the α/β-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.
biosynthesis, Neisseria meningitidis, Neisseria, capsular polysaccharide, capsule, polysialic acid, acyltransferase, meningitis
Structure type: homopolymer
Location inside paper: abstract, p.14, fig.7
Compound class: CPS
Contained glycoepitopes: IEDB_136794,IEDB_146100,IEDB_149174,IEDB_150075,IEDB_150759,IEDB_910420,SB_170,SB_171,SB_172,SB_84
Methods: SDS-PAGE, genetic methods, biochemical methods, immunoblotting
Enzymes that release or process the structure: OatC a/b-hydrolase
Biosynthesis and genetic data: biochemical data
Synthetic data: enzymatic
Related record ID(s): 23654, 23960, 23961
NCBI Taxonomy refs (TaxIDs): 135720
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
report error