CONFORMATION OF DENTAL SALIVARY MOLECULES

牙齿唾液分子的构象

• 批准号: 3221488
• 负责人: RONALD E LOOMIS
• 金额: $ 8.33万
• 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/3221488
• 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; pellicle; 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，并将继续 是对所选化合物的结构功能关系的阐明 唾液分子。用来研究这些问题的生物物理方法 大分子将提供有关分子性质的具体信息 它们的生物行为。如果一个人希望，这样的数据是必不可少的 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。三唾液 具有生物活性的分子将被检查。这个 首先是人腮腺唾液中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、膜的形成和钙的协调。第二， 我们将继续研究一种名为Statherin的富含酪氨酸的磷蛋白。 他汀类药物的主要生物学功能是调节 唾液和牙齿之间的钙磷平衡。最后， 酸性富含脯氨酸蛋白(APRP‘s)的结构将是 调查过了。已知的APRP类似的除虫菊酯是钙结合的 蛋白质。这三种唾液共有的生物学功能 分子是钙的配位。分子机制(S)和 这些需要结合的大分子中发生的构象变化 钙在很大程度上是未知的。关于免费的详细结构数据和 金属结合的唾液分子及其生物活性成分将 将被获得。最初，光学光谱技术(例如 荧光、紫外线和可见光、圆二向色性)将用于 辨别主体二级结构和三级结构。高分辨率核 然后将使用磁共振波谱来阐明空间 这些唾液分子的取向。比较光谱学 利用40Ca、适量稀土金属、113Cd和43Ca进行研究 将对金属结合的性质进行全面评估 在这些分子中存在S(Site)。最后，将对收集的数据进行提炼 使用计算机模拟技术计算原子核间距离和 从光谱研究中获得的扭角约束。这个 从这些数据中获得的结果将提供特定的信息 关于金属蛋白化学计量学，唾液的相互作用 分子自身(例如，双链或更高阶的自聚集)， 唾液分子与自身的相互作用(例如，双链或 高阶自聚集)，无金属的构象(S)和 金属结合分子，以及金属结合的精细结构 网站。最终将对数据进行整理，以确定这些唾液 分子有一种共同的钙配位方法。因此，结果是 从这些研究派生出来的将提供第一个相关性 唾液分子在原子水平上构象的生物活性 决议。