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Taxonomic group: fungi / Basidiomycota (Phylum: Basidiomycota)
Associated disease: infection due to Cryptococcus neoformans [ICD11: XN3EH

]

The structure was elucidated in this paper
NCBI PubMed ID: 37732210
Publication DOI: 10.1073/pnas.2315733121
Journal NLM ID: 7505876
Publisher: National Academy of Sciences
Correspondence: A. Casadevall <acasade1

jhu.edu>
Institutions: Laboratory of Bacterial Polysaccharides, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, Centre for Synthesis and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland

Cryptococcus neoformans is a fungal pathogen responsible for cryptococcosis and cryptococcal meningitis. The C. neoformans capsular polysaccharide and shed exopolysaccharide functions both as a key virulence factor and to protect the fungal cell from phagocytosis. Currently, a glycoconjugate of these polysaccharides is being explored as a vaccine to protect against C. neoformans infection. In this combined NMR and MD study, experimentally determined NOEs and J-couplings support a structure of the synthetic decasaccharide, GXM10-Ac3, obtained by MD. GXM10-Ac3 was designed as an extension of glucuronoxylomannan (GXM) polysaccharide motif (M2) which is common in the clinically predominant serotype A strains and is recognized by protective forms of GXM-specific monoclonal antibodies. The M2 motif is characterized by a 6-residue α-mannan backbone repeating unit, consisting of a triad of α-(1→3)-mannoses, modified by β-(1→2)-xyloses on the first two mannoses and a β-(1→2)-glucuronic acid on the third mannose. The combined NMR and MD analyses reveal that GXM10-Ac3 adopts an extended structure, with xylose/glucuronic acid branches alternating sides along the α-mannan backbone. O-acetyl esters also alternate sides and are grouped in pairs. MD analysis of a twelve M2-repeating unit polymer supports the notion that the GXM10-Ac3 structure is uniformly represented throughout the polysaccharide. This experimentally consistent GXM model displays high flexibility while maintaining a structural identity, yielding new insights to further explore intermolecular interactions between polysaccharides, interactions with anti-GXM mAbs, and the cryptococcal polysaccharide architecture.

NMR, structure, polysaccharide, Cryptococcus neoformans, Applied Biological Science, Biological Sciences - Biochemistry, Biophysics and Computational Biology, MD, Physical Sciences - Chemistry

Structure type: oligomer
Location inside paper: Fig. 1A, GXM10-Ac3 (Motif M2)
Trivial name: glucuronoxylomannan (GXM)
Compound class: CPS

Methods: 13C NMR, 1H NMR, NMR-2D, chemical synthesis, MD simulations, transglycosidic torsion calculations
Synthetic data: chemical
Comments, role: (preprint DOI:10.1101/2023.09.06.556507); the major polysaccharide GXM synthetic decasaccharide (GXM10-Ac3)
3D data: 3D structure of GXM10-Ac3

NCBI Taxonomy refs (TaxIDs): 5207
Show glycosyltransferases

There is only one chemically distinct structure:

CC(=O)OC[C@H]1O[C@H](OCCN)[C@@H](O[C@@H]2OC[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O[C@H]3O[C@H](COC(C)=O)[C@@H](O)[C@H](O[C@H]4O[C@H](COC(C)=O)[C@@H](O)[C@H](O[C@H]5O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]5O[C@@H]5OC[C@@H](O)[C@H](O)[C@H]5O)[C@@H]4O[C@@H]4OC[C@@H](O)[C@H](O)[C@H]4O)[C@@H]3O[C@@H]3O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]3O)[C@@H]2O[C@@H]2OC[C@@H](O)[C@H](O)[C@H]2O)[C@@H]1O

SVG MW SMILES 3D mol Ionize