CONFORMATION OF DENTAL SALIVARY MOLECULES

牙齿唾液分子的构象

• 批准号: 3221483
• 负责人: RONALD E LOOMIS
• 金额: $ 7.79万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3221483
• 关键词: calcium binding protein; calcium metabolism; chemical structure function; circular dichroism; computer simulation; fluorescence spectrometry; glycoproteins; human subject; macromolecule; mathematical model; metalloproteins; molecular dynamics; molecular pathology; parotid gland; phosphoproteins; proline; saliva; salivary glands; stoichiometry; tyrosine; ultraviolet spectrometry

The broad and long-term objective of this project has been and continues to be the elucidation of the structure function relationships in selected salivary molecules. The biophysical methodologies employed to study these macromolecules will provide specific information as to the molecular nature of their biological behavior. Such data is essential if one wishes to understand the processes governing both the normal and diseased states in the oral cavity. As part of our continuing studies. three salivary molecules with demonstrated biological activities will be examined. The first of these is the proline-rich glycoprotein from human parotid saliva (PRG). The biological functions of PRG include masticatory lubrication, bacterial binding, pellicle formation and calcium coordination. Secondly we will continue studying a tyrosine-rich phosphoprotein called statherin. The primary biological function of statherin is the regulation of the calcium-phosphate equilibrium between saliva and the tooth. Finally, the structure of the acidic proline-rich proteins (aPRP's) will be investigated. The aPRP's like stathrin are known to be calcium binding proteins. The biological function common to all three of these salivary molecules is that of calcium coordination. The molecular mechanism(s) and conformational changes occurring in these macromolecules required to bind calcium is largely unknown. Detailed structural data on the free and metal-bound salivary molecules as well as their bioactive constituents will be obtained. Initially, optical spectroscopic techniques (e.g. fluorescence, ultraviolet & visible, circular dichroism) will be used to discern bulk secondary and tertiary structures. High resolution nuclear magnetic resonance spectroscopy will then be used to elucidate the spatial orientations of these salivary molecules. Comparative spectroscopic investigations using 40Ca, appropriate rare earth metals, 113 Cd and 43Ca will be conducted to completely evaluate the nature of the metal binding site(s) in these molecules. Lastly, the collective data will be refined using computer modeling techniques with the internuclear distance and torsion angle constraints acquired from the spectroscopic studies. The results obtained from these data will provide specific information regarding metal protein stoichiometry, the interaction of the salivary molecules with themselves(e.g. duplex or higher order self aggregation), the interaction of the salivary molecules with themselves (e.g. duplex or higher order self-aggregation), the conformation(s) of the metal-free and metal-bound molecules, and the refined structures of the metal binding sites. The data will ultimately be collated to ascertain if these salivary molecules have a common method of calcium coordination. Thus, the results derived from these studies will provide the first correlations of biological activity with conformation in salivary molecules at atomic resolution.

该项目的广泛和长期目标一直是并继续 阐明选定的结构函数关系 唾液分子。 用于研究这些的生物物理方法 大分子将提供有关分子性质的特定信息 他们的生物行为。 如果一个人希望 了解管理正常状态和患病状态的过程 口腔。 作为我们继续学习的一部分。 三个唾液 将检查具有证明生物学活性的分子。 这 首先是人腮腺唾液中脯氨酸丰富的糖蛋白 （PRG）。 PRG的生物学功能包括咀嚼性润滑， 细菌结合，细胞形成和钙配位。 第二 我们将继续研究称为Statherin的富含酪氨​​酸的磷蛋白。 Statherin的主要生物学功能是调节 唾液和牙齿之间的磷酸钙平衡。 最后， 富含酸性脯氨酸的蛋白质（APRP）的结构将是 调查。 众所周知，APRP像白色的坚硬蛋白是钙结合 蛋白质。 这三个唾液的共有生物学功能 分子是钙配位的分子。 分子机制和 在这些大分子中发生的构象变化需要结合 钙在很大程度上未知。 有关免费和的详细结构数据 金属结合的唾液分子及其生物活性成分将 获得。 最初，光谱技术（例如 荧光，紫外线和可见的，圆形二色性）将用于 辨别批量的次要结构和第三级结构。 高分辨率核 然后，将使用磁共振光谱来阐明空间 这些唾液分子的方向。 比较光谱 使用40CA，合适的稀土金属，113 CD和43CA进行调查 将进行完全评估金属结合的性质 这些分子中的位点。 最后，集体数据将被完善 使用计算机建模技术与内部距离距离和 从光谱研究获得的扭转角约束。 这 从这些数据获得的结果将提供特定的信息 关于金属蛋白化学计量法，唾液的相互作用 与自己的分子（例如双链或高阶自聚集）， 唾液分子与自己的相互作用（例如双链或 高阶自聚集），无金属的构象和 金属结合的分子和金属结合的精制结构 站点。 最终将整理数据以确定这些唾液是否是否 分子具有钙配位的通用方法。 因此，结果 从这些研究中得出的将提供的第一个相关性 生物学活性与原子唾液分子的构象 解决。