Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: meningitis [ICD11:
1D01 
];
infection due to Neisseria meningitidis [ICD11:
XN1DV ]
NCBI PubMed ID: 19525232Publication DOI: 10.1074/jbc.M109.006049Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: natalie
byron.biochem.ubc.ca
Institutions: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
The neuroinvasive pathogen Neisseria meningitidis has 13 capsular serogroups, but the majority of disease is caused by only 5 of these. Groups B, C, Y, and W-135 all display a polymeric sialic acid-containing capsule that provides a means for the bacteria to evade the immune response during infection by mimicking host sialic acid-containing cell surface structures. These capsules in serogroups C, Y, and W-135 can be further acetylated by a sialic acid-specific O-acetyltransferase, a modification that correlates with decreased immunoreactivity and increased virulence. In N. meningitidis serogroup Y, the O-acetylation reaction is catalyzed by the enzyme OatWY, which we show has clear specificity toward the serogroup Y capsule ([Glc-(α1→4)-Sia](n)). To understand the underlying molecular basis of this process, we have performed crystallographic analysis of OatWY with bound substrate as well as determined kinetic parameters of the wild type enzyme and active site mutants. The structure of OatWY reveals an intimate homotrimer of left-handed beta-helix motifs that frame a deep active site cleft selective for the polysialic acid-bearing substrate. Within the active site, our structural, kinetic, and mutagenesis data support the role of two conserved residues in the catalytic mechanism (His-121 and Trp-145) and further highlight a significant movement of Tyr-171 that blocks the active site of the enzyme in its native form. Collectively, our results reveal the first structural features of a bacterial sialic acid O-acetyltransferase and provide significant new insight into its catalytic mechanism and specificity for the capsular polysaccharide of serogroup Y meningococci.
Neisseria meningitidis, virulence, O-acetylation, sialic acid, acetyltransferase, OatWY, serogroup Y
Structure type: polymer chemical repeating unit
Location inside paper: abstract, p.24502 fig.1
Trivial name: repeating unit, type Y polysaccharide, oligosaccharide repeating unit
Compound class: CPS, O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_136794,IEDB_142488,IEDB_144998,IEDB_146100,IEDB_146664,IEDB_148489,IEDB_149174,IEDB_158547,IEDB_983931,SB_170,SB_171,SB_172,SB_192,SB_84
Methods: genetic methods, biochemical methods, molecular modeling, crystallization
Biological activity: kinetic data
3D data: 3D data
Related record ID(s): 3243, 7525, 23338, 23961
NCBI Taxonomy refs (TaxIDs): 648194Reference(s) to other database(s): GTC:G10851PI, GlycomeDB:
25956
Show glycosyltransferases
There is only one chemically distinct structure:
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