NEAR ULTRAVIOLET RAMAN STUDIES OF CYTOCHROME P450

描述：（改编自申请人的摘要） 建议是扩展对结构和功能的理解 利用拉曼光谱对细胞色素P450和其他血红素蛋白系统的研究 飞秒相干光谱（FCS）， 直接探测诱导的相干蛋白质/辅因子振动运动 与生化反应相关的电子跃迁。 总体而言，该项目具有广泛的健康相关影响 尤其是P450和血红素。许多化疗 P450可代谢多环致癌物 系统.此外，所有涉及P450蛋白的代谢紊乱 与这项工作，因为一个基本的了解，积极的网站 P450在分子水平上的结构和功能将导致 更好地了解这些疾病的治疗， 任何水平。这些研究将采用光谱测量， 允许键，反应特定的电子和电子-核耦合 要从X射线结构的组合提取的参数， FCS数据。仔细研究反应和场驱动相干 作为温度、粘度和蛋白质扰动的函数， 为了更好地分配和理解的性质， 在反应过程中形成的相干态。时间 解析的蛋白质动力学和动力学将在许多阶上进行 的量级，从飞秒到千秒，和新颖的双脉冲 动力学实验将用于探索快速反应 亚群的集合，使蛋白质构象 直接显示了相互转换时间。理论工作涉及 血红素蛋白中的配体结合和解离，反应相干性， 电子转移，共振光物质相互作用也将是 追求。

DESCRIPTION: (adapted from applicant's abstract) The aim of this proposal is to extend the understanding of the structure and function of cytochrome P450 and other heme protein systems by using Raman spectroscopy and femtosecond coherence spectroscopy (FCS), which directly probes the coherent protein/cofactor vibrational motion induced by electronic transitions associated with biochemical reactions. Overall, this project has a wide range of health related implications involving P450 in particular and hemes in general. Many chemotherapeutic agents as well as polycyclic carcinogens are metabolized by P450 systems. Moreover, all metabolic disorders involving a P450 protein relate to this work since a fundamental understanding of the active site structure and function of P450 at the molecular level will result in better insight for those concerned with treatment of these disorders at any level. These studies will employ spectroscopic measurements that allow key, reaction specific electronic and electron-nuclear coupling parameters to be extracted from the combination of x-ray structure and FCS data. Careful studies of the reaction and field driven coherences as a function of temperature, viscosity, and protein perturbations will be carried out in order to better assign and understand the nature of the coherent states that are formed as the reactions proceed. Time resolved protein dynamics and kinetics will be followed over many orders of magnitude, from femtoseconds to kiloseconds, and novel double-pulse kinetics experiments will be used to probe rapidly reacting subpopulations of the ensemble so that protein conformational interconversion times are directly revealed. Theoretical work involving ligand binding and dissociation in heme proteins, reaction coherence, electron transfer, and resonant light-matter interactions will also be pursued.