SPECTROSCOPY AND FUNCTION OF REDOX METALLOPROTEINS

这个项目的中心目标是阐明 影响氧化还原活性中心功能的因素 金属蛋白。这些蛋白质对所有生物体都是必不可少的。他们 普遍存在于发生生物电子转移的过程中， 例如在呼吸作用、光合作用、小分子激活 分子，以及有机底物的氧化。足够 要了解这些蛋白质的功能是不可能的，除非 控制活性金属位置行为的原则是 明白了。我们建议为关键系统建立这些原则 具有普遍意义的。这些原则随后可应用于氧化还原。 金属蛋白是一类总称。关键问题包括以下几点。 氧化还原金属蛋白如何识别、接纳和控制结合 底物的？底物激活是如何完成的？你是如何 蛋白质进行便捷的电子转移，以及它们如何修饰或 开关电子转移动力学和热力学响应于 功能要求和环境条件？他们的表现如何？ 质子抽运储能等耦合功能？ 我们解决这些问题的一般方法是 光谱学。我们之前已经强调过振动 光谱分析，但我们的经验表明，复杂的金属蛋白 问题必须通过许多不同的技术来解决。因此，这 提案比它的前身更笼统，标题反映了 这扩大了重点。 在过去的授权期内，我们制定了具体的假设 金属的不稳定配位化学(“配体穿梭”) 氧化还原金属蛋白中心可能在活性部位起关键作用 功能。该提案的很大一部分都集中在测试上 这些假说使用了血红素-铜氧化酶作为靶标系统。我们 还提出了针对其他领域重大问题的研究 氧化还原金属蛋白。其中包括新型远红光拉曼的应用 具有极低吸收率的生色团的铜蛋白质技术 能量(例如一氧化二氮还原酶)和红外研究 镍氢酶的官能化和光化学反应。

The central objective of this project is to elucidate the fundamental factors that influence the function of the active sites of redox metalloproteins. These proteins are essential to all organisms. They are ubiquitous in processes where biological electron transfer occurs, for example in respiration, photosynthesis, activation of small molecules, and the oxygenation of organic substrates. Adequate understanding of the function of these proteins cannot be expected unless the principles governing the behavior of the active metal sites are understood. We propose to establish these principles for key systems having general significance. The principles may then be applied to redox metalloproteins as a general class. Key issues include the following. How do redox metalloproteins recognize, admit, and control the binding of substrate? How is substrate activation accomplished? How do the proteins carry out facile electron transfer, and how do they modify or switch electron transfer dynamics and thermodynamics in response to functional requirements and ambient conditions? How do they perform coupled functions such as energy storage by proton pumping? Our general approaches to these problems are various techniques in optical spectroscopy. We have previously emphasized vibrational spectroscopies, but our experience has shown that complex metalloprotein issues must be addressed by many different techniques. Accordingly this proposal is more general than its predecessors, and the title reflects this broadened emphasis. During the past grant period we have developed specific hypotheses as to how labile coordination chemistry ("ligand shuttling") at the metal centers of redox metalloproteins may play key roles in active site function. A significant fraction of this proposal is focused on testing these hypotheses using the heme-copper oxidases as target systems. We also propose studies that are directed at significant issues in other redox metalloproteins. These include application of novel far-red Raman technique to copper proteins having chromophores that absorb at very low energy (e.g. the nitrous oxide reductases) and infrared studies of the functional and photochemical reactions of nickel hydrogenases.