Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: bacterial septicemia [ICD11:
MA15.Y 
];
meningitis [ICD11:
1D01 ];
infection due to Neisseria meningitidis [ICD11:
XN1DV ]
NCBI PubMed ID: 26598987Publication DOI: 10.1016/j.carres.2015.10.016Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: xiichen
ucdavis.edu
Institutions: Department of Chemistry, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA
Neisseria meningitidis serogroup A non-hydrolyzing uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase (NmSacA) catalyzes the interconversion between UDP-GlcNAc and uridine 5'-diphosphate-N-acetylmannosamine (UDP-ManNAc). It is a key enzyme involved in the biosynthesis of the capsular polysaccharide [-6ManNAcĪ±1-phosphate-]n of N. meningitidis serogroup A, one of the six serogroups (A, B, C, W-135, X, and Y) that account for most cases of N. meningitidis-caused bacterial septicemia and meningitis. N. meningitidis serogroup A is responsible for large epidemics in the developing world, especially in Africa. Here we report that UDP-ManNAc could be used as a substrate for C-terminal His6-tagged recombinant NmSacA (NmSacA-His6) in the absence of UDP-GlcNAc. NmSacA-His6 was activated by UDP-GlcNAc and inhibited by 2-acetamidoglucal and UDP. Substrate specificity study showed that NmSacA-His6 could tolerate several chemoenzymatically synthesized UDP-ManNAc derivatives as substrates although its activity was much lower than non-modified UDP-ManNAc. Homology modeling and molecular docking revealed likely structural determinants of NmSacA substrate specificity. This is the first detailed study of N. meningitidis serogroup A UDP-GlcNAc 2-epimerase.
Neisseria meningitidis, capsular polysaccharide, epimerization, modeling, meningitis, UDP-GlcNAc, UDP-GlcNAc 2-epimerase, UDP-ManNAc
Structure type: homopolymer
Location inside paper: p.18
Trivial name: oligosaccharide repeating unit, repeating unit of capsular polysaccharide
Compound class: CPS, O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_149549,IEDB_149550,IEDB_149551,IEDB_149552
Methods: 13C NMR, 1H NMR, NMR-2D, SDS-PAGE, kinetics assays, 31P NMR, ESI-MS, chemical synthesis, genetic methods, biochemical methods, enzyme assay, chemoenzymatic synthesis
Biosynthesis and genetic data: the cloning, expression, characterization of NmSacA, an N. meningitidis serogroup A non-hydrolyzing UDP-GlcNAc 2-epimerase
3D data: 3D data
NCBI Taxonomy refs (TaxIDs): 65699Reference(s) to other database(s): GTC:G20238HN, GlycomeDB:
25952
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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