CONFORMATION OF DENTAL SALIVARY MOLECULES

该项目的广泛和长期目标一直是并将继续是 阐明了所选化合物的结构与功能关系， 唾液分子 生物物理学方法用于研究这些 大分子将提供关于分子性质的特定信息 他们的生物行为。 这些数据是必不可少的，如果一个人希望 了解控制正常和疾病状态的过程， 口腔。 作为我们继续学习的一部分。 三唾液 将检查具有已证实的生物活性的分子。 的 第一种是来自人腮腺唾液的富含脯氨酸的糖蛋白 （PRG）。 PRG的生物学功能包括咀嚼润滑， 细菌结合、膜形成和钙协调。 其次 我们将继续研究一种富含酪氨酸的磷蛋白，称为statherin。 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 富含脯氨酸的酸性蛋白质（aPRP）的结构将是 研究了 已知aPRP与司他林一样与钙结合 proteins. 这三种唾液共同的生物学功能 分子是钙的协调。 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。 详细的结构数据上的自由和 金属结合的唾液分子以及它们的生物活性成分将 获得。 最初，光学光谱技术（例如， 荧光，紫外和可见光，圆二色性）将用于 辨别大量的二级和三级结构。 高分辨率核 磁共振波谱将用于阐明空间 这些唾液分子的方向。 比较光谱学 使用40Ca、适当的稀土金属、113Cd和43Ca进行的调查 将进行全面评估的性质，金属结合 这些分子中的位点。 最后，将对收集的数据进行细化 利用计算机模拟技术， 扭转角的限制，从光谱研究中获得。 的 从这些数据中获得的结果将提供具体信息 关于金属蛋白化学计量，唾液 分子与其自身（例如双链体或更高级的自聚集）， 唾液分子与自身的相互作用（例如双链体或 高阶自聚集），无金属和 金属结合的分子，以及金属结合的精细结构 网站. 这些数据最终将被整理，以确定这些唾液是否 分子具有钙配位的共同方法。 因此，结果 从这些研究中得出的结论将提供以下方面的第一个相关性： 唾液分子在原子水平上的构象与生物活性 分辨率

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.