US-UK Cooperative Research: Pulse Radiolysis Studies of Xanthine Oxidase

该奖项将支持俄亥俄州立大学C. Russell Hille博士和英国米德尔塞克斯芒特弗农医院格雷实验室Robert F. Anderson博士之间的合作研究。研究人员将对牛奶黄嘌呤氧化酶的氧化还原行为进行研究，黄嘌呤氧化酶是一种定义明确的代谢重要酶。黄嘌呤氧化酶含有四个位点，能够在催化周转过程中可逆地接受还原等价物。总共需要六个减少当量才能完全减少所有这些中心。因此，这种酶提供了一个很好的机会来研究控制生物电子转移的原理，作为一个系统，在这个系统中，位点彼此保持固定的距离和方向，在一个或多或少刚性的多肽基质中。在这项工作中使用的主要技术是脉冲辐射分解，这项技术在研究生化氧化还原问题方面的应用尚未得到广泛的认识。预计这项工作的结果将不仅仅对黄嘌呤氧化酶有影响，而且将证明与其他更复杂的系统相关，例如发生在线粒体和叶绿体中的系统。脉冲辐射分解在蛋白质内和蛋白质间电子转移研究中的普遍适用性的证明，将为研究这些基本生物过程提供一种强有力的新技术。这位英国合作者是公认的脉冲辐射分解专家，长期以来一直对脉冲辐射分解应用于生物学重要分子中电子转移过程的研究感兴趣。该项目还将受益于格雷实验室现有的最先进的脉冲辐射分解设备。希尔博士的专长是氧化还原酶学和酶动力学。

This award will support collaborative research between Dr. C. Russell Hille, Ohio State University and Dr. Robert F. Anderson, Gray Laboratory, Mount Vernon Hospital, Middlesex, England. The investigators will carry out a study of the oxidation-reduction behavior of milk xanthine oxidase, a well-defined enzyme of importance in metabolism. Xanthine oxidase contains four sites capable of reversibly accepting reducing equivalents during catalytic turnover. A total of six reducing equivalents are required to fully reduce all these centers. The enzyme thus provides an excellent opportunity to examine the principles governing biological electron transfer as a system in which the sites are held at a fixed distance and orientation to one another, within a more or less rigid polypeptide matrix. The principle technique to be used in this work is pulse radiolysis, a technique whose utility in studying biochemical oxidation-reduction problems is not widely appreciated. It is anticipated that the results of this work will have implications beyond xanthine oxidase alone, and will prove relevant to other more complex systems, such as those occurring in the mitochondrion and chloroplast. The demonstration of the general suitability of pulse radiolysis in the study of intra-and interprotein electron transfer would provide the field with a powerful new technique for the study of these fundamental biological processes. The British collaborator is a recognized expert in pulse radiolysis and has a long standing interest in the application of pulse radiolysis to the study of electron transfer processes in biologically important molecules. The project will also benefit from state-of-the art pulse radiolysis facilities available at the Gray Laboratory. Dr. Hille's expertise is in oxidation-reduction enzymology and enzyme kinetics.