STRUCTURAL ROLE OF GLYCANS IN GONADOTROPIN HORMONES

聚糖在促性腺激素中的结构作用

• 批准号: 6653564
• 负责人: JOHN GLUSHKA
• 金额: $ 28.8万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6653564
• 关键词: AIDS; biological products; biomedical resource; carbohydrates; immunology; infection; inflammation; lymphatic system; microorganism; nuclear magnetic resonance spectroscopy; structural biology; technology /technique; virus

Cryptococcus neoformans, the major etiological agent of Cryptococcosis, is a primary cause of opportunistic infections in AIDS patients. Four serotypes (A-D) of C. neoformans are distinguished; they differ in the structure of the glucuronoxylomannans (GXMs), capsular polysaccharides on their outer surface. Primary structural characterization of these GXMs is the first step in understanding the epitope specificity corresponding to the individual serotypes. The primary structure, conformation, and dynamics of the GXM serotype D, labeled with 13C, was studied by NMR spectroscopy. In order to aid the analysis, molecular dynamics (MD) simulations are being performed on the pentasaccharide repeating unit of serotype D using the GLYCAM 93 parameter set developed for AMBER. NOE build-up rates are being used in a restrained MD protocol to derive a solution structure of this repeating unit. Alternative approaches to comparing the results of long (~ ns) MD simulations to NMR data are being explored. Analysis of the 13C-NMR heteronuclear relaxation rates are being analyzed by the "model-free" formalism of Lipari and Szabo to reveal internal motions in the polysaccharide that occur on a timescale faster than the rotation correlation time of the molecule. We are mapping the spectral density of the molecule through a more detailed measurement of the relaxation rates of different coherences to compare the results with the Lipari-Szabo formalism an d thus evaluate its usefulness in studying the dynamics of polysaccharides. This conformational analysis of the repeating unit of serotype D will set the stage for attempting similar studies on the most virulent serotype A strain of C. neoformans.

加密环球机构，主要病因的主要病因 隐球菌病是艾滋病机会感染的主要原因 患者。 区分了四种新生梭菌的血清型（A-D）； 它们在葡萄糖醛氧基瘤（GXM）的结构上有所不同， 其外表面上的囊状多糖。 主要结构 这些GXM的表征是理解的第一步 表位特异性对应于单个血清型。 这 GXM血清型D的主要结构，构象和动力学， 通过NMR光谱研究了用13C标记的13C。 为了帮助 分析，分子动力学（MD）模拟正在进行 在五糖重复单元的血清型D上，使用聚糖 93为琥珀开发的参数集。 Noe的增加率正在 在受约束的MD协议中用于得出的解决方案结构 这个重复单元。 比较结果的替代方法 正在探索长（〜ns）的MD模拟NMR数据。 正在分析13C-NMR异核松弛率 通过Lipari和Szabo的“无模型”形式主义分析以揭示 在时间尺度上发生的多糖的内部运动 比分子的旋转相关时间快。 我们是 通过更详细的绘制分子的光谱密度 测量不同连贯的放松率以比较 lipari-szabo形式主义和d的结果评估了其 在研究多糖的动力学方面有用。 这 血清型D重复单元的构象分析将设置 尝试对最有毒血清型的类似研究的阶段 Neoformans的菌株。