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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,2,13]]},"abstract":"<jats:p>\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    is a fungal pathogen responsible for cryptococcosis and cryptococcal meningitis. The\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    \u2019 capsular polysaccharide and its shed exopolysaccharide function both as key virulence factors and to protect the fungal cell from phagocytosis. Currently, a glycoconjugate of these polysaccharides is being explored as a vaccine to protect against\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    infection. In this study, NOE and\n                    <jats:italic>J<\/jats:italic>\n                    -coupling values from NMR experiments were consistent with a converged structure of the synthetic decasaccharide, GXM10-Ac\n                    <jats:sub>3<\/jats:sub>\n                    , calculated from MD simulations. GXM10-Ac\n                    <jats:sub>3<\/jats:sub>\n                    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 a hexasaccharide with a three-residue \u03b1-mannan backbone, modified by \u03b2-(1\u21922)-xyloses (Xyl) on the first two mannoses (Man) and a \u03b2-(1\u21922)-glucuronic acid (GlcA) on the third Man. Combined NMR and MD analyses reveal that GXM10-Ac\n                    <jats:sub>3<\/jats:sub>\n                    adopts an extended structure, with Xyl\/GlcA branches alternating sides along the \u03b1-mannan backbone.\n                    <jats:italic>O<\/jats:italic>\n                    -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-Ac\n                    <jats:sub>3<\/jats:sub>\n                    structure is uniformly represented throughout the polysaccharide. This derived GXM model displays high flexibility while maintaining a structural identity, yielding insights to further explore intermolecular interactions between polysaccharides, interactions with anti-GXM mAbs, and the cryptococcal polysaccharide architecture.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2315733121","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T13:40:36Z","timestamp":1707399636000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["The structure of a\n                    <i>Cryptococcus neoformans<\/i>\n                    polysaccharide motif recognized by protective antibodies: A combined NMR and MD study"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0459-1392","authenticated-orcid":false,"given":"Audra A.","family":"Hargett","sequence":"first","affiliation":[{"name":"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 20993"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5773-9127","authenticated-orcid":false,"given":"Hugo F.","family":"Azurmendi","sequence":"additional","affiliation":[{"name":"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 20993"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor J.","family":"Crawford","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205"},{"name":"Centre for Synthesis and Chemical Biology, University College Dublin, Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie P.","family":"Wear","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8273-4918","authenticated-orcid":false,"given":"Stefan","family":"Oscarson","sequence":"additional","affiliation":[{"name":"Centre for Synthesis and Chemical Biology, University College Dublin, Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9402-9167","authenticated-orcid":false,"given":"Arturo","family":"Casadevall","sequence":"additional","affiliation":[{"name":"W. 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