NEAR ULTRAVIOLET RAMAN STUDIES OF CYTOCHROME P450

我们观察到了详细的、信息量丰富的血红素共振拉曼光谱。 细胞色素P450、细胞色素c、肌红蛋白和血红蛋白等蛋白质。 激光在深蓝和近紫外共振吸收中的激发 条带导致与血红素相关的信号强度大大增强 修复组。我们的目标是扩大我们对结构和 细胞色素P450和其他血红素蛋白系统的功能 拉曼和其他快速发展的基于激光的光谱仪。这些 研究将使用拉曼激发分布测量，以允许关键 要从组合中提取的电子-核耦合参数 吸收和拉曼数据。对吸收和拉曼光谱的仔细研究 线型也将作为温度的函数进行。样本 涉及定点突变、pH和光泵浦的微扰 也是预定的。时间分辨蛋白质动力学将在这两个实验室中进行研究 纳秒和皮秒制度。配体的光解与电子 伴随热弛豫和非辐射衰变的输运现象 将对过程进行调查。肌红蛋白和肌红蛋白的单晶样品 细胞色素P450cam也将作为取向和 激发波长。诱导z-极化电荷的各种配体 转移激发将被复合到晶体中，以便于检查 极化张量的细节。涉及到的理论工作 配基结合到血红素蛋白，电子转移和共振光- 物质的相互作用也将被研究。协作实验 涉及微波导电性、电子自旋共振和深 将启动紫外拉曼散射。这个整体项目有 涉及细胞色素P450的广泛的健康相关影响 特殊的和一般的血红素蛋白。许多化疗药物 药物和多环致癌物都是由P450系统代谢的。 此外，所有涉及P450蛋白的代谢紊乱都必须与 这项研究。当然，对活动站点有基本的了解 P450在分子水平上的结构和功能将导致 对那些关心这些疾病治疗的人有更好的洞察力 水平。

We have observed detailed and informative resonance Raman spectra from heme proteins such as cytochrome P450, cytochrome c, myoglobin and hemoglobin. Laser excitation in the deep blue and near ultraviolet resonant absorption bands leads to greatly enhanced signal intensities associated with the heme prosthetic group. We aim to extend our understanding of the structure and function of cytochrome P450 and other heme protein systems by the use of Raman and other rapidly developing laser based spectroscopies. These studies will employ Raman excitation profile measurements that allow key electron-nuclear coupling parameters to be extracted from the combined absorption and Raman data. Careful studies of the absorption and Raman lineshapes will also be carried out as a function of temperature. Sample perturbations involving site directed mutagenesis, pH and optical pumping are also scheduled. Time resolved protein dynamics will be studied in both the nanosecond and picosecond regimes. Ligand photolysis and electron transport phenomena along with thermal relaxation and non-radiative decay processes will be investigated. Single crystal samples of myoglobin and cytochrome P450cam will also be studied as a function of orientation and excitation wavelength. Various ligands that induce z-polarized charge transfer excitations will be complexed to the crystals in order to examine the details of the polarizability tensor. Theoretical work involving ligand binding to heme proteins, electron transfer and resonant light- matter interactions will also be pursued. Collaborative experiments involving microwave conductivity, electron spin resonance and deep ultraviolet Raman scattering will be initiated. This overall project has wide range of health related implications involving cytochrome P450 in particular and heme proteins in general. Many chemotherapeutic agents as well as polycyclic carcinogens are metabolized by P450 systems. Moreover, all metabolic disorders involving a P450 protein must relate to this research. Certainly a fundamental understanding of the active site structure and function of P450 at the molecular level will result in a better insight for those concerned with treatment of these disorders at any level.