Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
Associated disease: infection due to Cryptococcus neoformans [ICD11:
XN3EH 
]
NCBI PubMed ID: 8294434Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Institutions: Department of Microbiology, University of Nevada, Reno 89557
Monoclonal antibodies that react with the capsular polysaccharide, termed glucuronoxylomannan (GXM), of Cryptococcus neoformans have potential roles in the diagnosis, monitoring of disease progress, and immunotherapy of cryptococcal GXM of all four serotypes. A molecular model of the Fab fragment of monoclonal antibody 439 was constructed from the amino acid sequence and a template antibody molecule, Fab 4-4-20. A tryptophan is present on the surface between light chain CDR3 and heavy chain CDR3 in the putative binding site. This tryptophan residue proved to be a reporter group, and a fluorescence study of Fab 439 was performed to analyze the interaction between cryptococcal GXM and Fab 439. Binding of the polysaccharide enhanced the intrinsic fluorescence and caused a blue shift in the emission maximum, indicating that the environment of a tryptophan changes from a polar to less polar environment. This is consistent with the loss of water from the binding site caused by the binding of antigen. This interpretation was confirmed by acrylamide quenching, which showed that 1 less tryptophan was exposed to solvent in the Fab-GXM complex than in free Fab. Fluorescence titration was used to determine binding and dissociation constants (KD). The apparent KD values for serotypes A-C were approximately the same; the KD for serotype D GXM was 5-11-fold greater. De-O-acetylation of serotype A GXM produced a 31-fold increase in the KD, indicating that the O-acetyl groups are important, but not essential, for binding. Carboxyl groups appear to be essential for strong binding because the KD for carboxyl-reduced GXM was so large that it could not be determined.
Structure type: structural motif or average structure
Location inside paper: scheme 1, D
Trivial name: glucuronoxylomannan (GXM), glucuronoxylomannan (GXM) Motif M1
Compound class: CPS, cell wall polysaccharide, glucuronoxylomannan
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_140116,IEDB_140630,IEDB_144983,IEDB_145668,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
Methods: alkaline hydrolysis, fluorescence analysis of antibody-polysaccharide complex
Comments, role: a model structure of Cryptococcus neoformans serotype D; isolate 24067, strains 529 and 52 (serotype D) were used in the work. Chemical repeating unit frame was shifted in annotation for compatibility with structures elucidated by MS [Eukaryotic Cell 2007, 6: 1464-1473].
Related record ID(s): 50826, 110711, 130611, 136940, 136941, 136942, 143856, 148625
NCBI Taxonomy refs (TaxIDs): 40410Reference(s) to other database(s): GTC:G53406VG, CCSD:
31674, CBank-STR:13359
Show glycosyltransferases
There is only one chemically distinct structure:
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(later renamed to: Cryptococcus neoformans var. neoformans)