MODEL SYSTEMS FOR FLAVOENZYME ACTIVITY

黄素酶是利用黄素辅因子（FAD或FMN） 影响氧化还原转化和电子转移。这些酶 发挥各种重要的生物学作用，包括 代谢、生物合成和电子传递。之多样 这些蛋白质催化的过程同样令人印象深刻，包括 这种发散转化如硫醇和胺氧化， 芳族羟基化和脂肪酸脱氢。前几 研究，我们已经使用模型系统来探索的基本方面， 黄素酶的功能，特别是酶辅因子的作用 调节黄素氧化还原过程的相互作用。这些模型 使我们能够分离和量化特定的相互作用， 它们在决定黄素酶功能中的作用。 在我们提出的研究中，我们将使用 合成受体与化学物质协同应用， 电化学、光谱和计算技术。化学 研究中，我们将合成受体，探索识别的作用 生物医学关键的机制和能量学过程 硫醇脱氢酶同时，我们将利用 电化学技术直接量化氧化还原的能量学 流程.在这些研究中，我们将合成受体， 确定"传统"非共价相互作用的作用，包括 氢键，在调节黄素氧化还原过程。我们将 也创造受体，以确定微观和宏观的作用， 偶极对黄素氧化还原过程的影响。这些调查虽然集中在 在黄素氧化还原系统，也将提供洞察一般 静电在酶功能中的作用问题。 在光谱学上，我们将采用双管齐下的方法来研究 黄素类首先，我们将研究识别对 黄素和黄素自由基的NMR、EPR和ENDOR谱。我们将 然后使用这些光谱作为计算方法的校准。 从这两种方法的协同作用，我们将能够量化 个体相互作用对基本性质的影响，包括 电荷和自旋密度分布。使用我们的模型系统作为 基准，我们也将能够扩大我们的信心， 计算研究到实际的酶系统。

Flavoenzymes are proteins that use the flavin co-factor (FAD or FMN) to effect redox transformations and electron transfer. These enzymes function in a variety of essential biological roles, including metabolism, biosynthesis, and electron transport. The diversity of processes catalyzed by these protein is equally impressive, encompassing such divergent transformations such as thiol and amine oxidations, aromatic hydroxylation, and fatty acid dehydrogenation. In previous research, we have used model systems to explore fundamental aspects of flavoenzyme function, in particular the role of enzyme-co-factor interactions in modulating flavin redox processes. These models have allowed us to isolate and quantify specific interactions, and establish their role in determining flavoenzyme function. In our proposed research, we will extend these studies, using a synergistic application of synthetic receptors with chemical, electrochemical, spectroscopic and computational techniques. In chemical studies, we will synthesize receptors to explore the role of recognition processes in the mechanisms and energetics of the biomedically crucial thiol dehydrogenases. Concurrently, we will exploit the ability of electrochemical techniques to directly quantify the energetics of redox processes. In these investigations, we will synthesize receptors to determine the role of "traditional" non-covalent interactions, including hydrogen bonding, in the modulation of flavin redox processes. We will also create receptors to ascertain the role of micro- and macroscopic dipoles on flavin redox processes. These investigations, while focusing on the flavin redox system, will also provide insight into the general issue of the function of electrostatics in enzyme function. Spectroscopically, we will use a two-pronged approach to the study of flavin species. First, we will investigate the effects of recognition on the NMR, EPR and ENDOR spectra of flavins and flavin radicals. We will then use these spectra as calibration for computational methodology. From the synergy of these two methods, we will be able to quantify the effects of individual interactions on fundamental properties, including charge and spin density distributions. Using our model systems as a benchmark, we will also be able to extend with confidence our computational studies to actual enzymatic systems.