Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
Organ / tissue: capsuleAssociated disease: infection due to Cryptococcus neoformans [ICD11:
XN3EH 
];
infection due to Cryptococcus gattii [ICD11:
XN0LE 
]
Journal NLM ID: 2985120RWWW link: http://jb.asm.org/content/181/17/5482.longPublisher: American Society for Microbiology
Correspondence: doering

borcim.wustl.edu
Institutions: Department of Pharmacology, Cornell University Medical College, New York, New York
The major virulence factor of the pathogenic fungusCryptococcus neoformans is an extensive polysaccharide capsule which surrounds the cell. Almost 90% of the capsule is composed of a partially acetylated linear α-1,3-linked mannan substituted with D-xylose and D-glucuronic acid. A novel mannosyltransferase with specificity appropriate for a role in the synthesis of this glucuronoxylomannan is active in cryptococcal membranes. This membrane-associated activity transfers mannose in vitro from GDP-mannose to an α-1,3-dimannoside acceptor, forming a second α-1,3 linkage. Product formation by the transferase is dependent on protein, time, temperature, divalent cations, and each substrate. It is not affected by amphomycin or tunicamycin but is inhibited by GDP and mannose-1-phosphate. The described activity is not detectable in the model yeast Saccharomyces cerevisiae, consistent with the absence of a similar polysaccharide structure in that organism. A second mannosyltransferase from C. neoformans membranes adds mannose in α-1,2 linkage to the same dimannoside acceptor. The two activities differ in pH optimum and cation preference. While the α-1,2 transferase does not have specificity appropriate for a role in glucuronoxylomannan synthesis, it may participate in production of mannoprotein components of the capsule. This study suggests two new targets for antifungal drug discovery.
Structure type: structural motif or average structure
Location inside paper: fig. 1
Compound class: glucuronoxylomannan
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_1394182,IEDB_140116,IEDB_140630,IEDB_144983,IEDB_145668,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_2270799,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
Methods: enzymatic digestion, enzymatic assay, radiolabelling
Synthetic data: enzymatic
Comments, role: major repeating unit
NCBI Taxonomy refs (TaxIDs): 37769Reference(s) to other database(s): GTC:G28901JS
Show glycosyltransferases
There are too many chemically distinct structures (~16384), so only one is shown:
-3)[bDXylp(1-2)]aDManp(1-3)[bDXylp(1-4),bDGlcpA(1-2)]aDManp(1-3)[bDXylp(1-2)]aDManp(1-