Presidential Young Investigator Award/Structural and Functional Studies of Metalloenzyme Active Sites

这笔赠款为总统青年研究人员奖提供剩余三年的资金。该研究项目属于生物无机化学的一般领域，涉及金属酶的活性中心结构和决定金属蛋白之间电子转移速率的因素。为了探索距离对电子转移速率的影响，将开发碳二亚胺辅助的氧化还原活性过渡金属络合物与细胞色素c的赖氨酸、谷氨酸或天冬氨酸残基的连接的一般反应。这种方法将产生许多在血红素和连接的络合物之间具有不同距离的单一修饰的衍生物，因此，分子内电子转移速率的测量将产生该速率的距离依赖关系。这种方法将扩展到其他蛋白质，如肌红蛋白和其他细胞色素。另一个子项目将涉及S-甲基辅酶-M还原酶含镍修复基团的光谱表征，该酶在产甲烷细菌的能量产生周期中催化甲烷的产生。用磁化率、核磁共振、共振拉曼光谱和X射线吸收光谱确定酶中与镍结合的轴向配体的性质。

This grant provides the remaining three years of funding for a Presidential Young Investigator Award. The research project is in the general area of bioinorganic chemistry and is concerned with the active site structures of metalloenzymes and with the factors which determine the rates of electron transfer between metalloproteins. To probe the effects of distance on rates of electron transfer, general reactions will be developed for the carbodiimide-assisted attachment of redox active transition metal complexes to lysine, glutamate, or aspartate residues of cytochrome c. This approach will generate a number of singly-modified derivatives with varying distances between the heme and the attached complex, so that measurement of intramolecular electron transfer rates will yield the distance dependence of that rate. This approach will be extended to other proteins such as myoglobin and other cytochromes. Another subproject will involve spectroscopic characterization of the Ni-containing prosthetic group of S-methyl coenzyme-M reductase, the enzyme which catalyzes the production of methane in the energy-producing cycle of methanogenic bacteria. The nature of the axial ligands bound to Ni in the enzyme will be determined using magnetic susceptibility, NMR, resonance Raman spectroscopy and x-ray absorption spectroscopy.