Conformational Dynamics and Hole-hopping in Metalloprotein Electron Transfer

这个奖项在无机，生物无机和有机化学计划支持教授布赖恩R。康奈尔大学的起重机研究细胞色素c过氧化物酶（CcP）和细胞色素c（Cc）之间的远程电子转移，以确定分子缔合，构象动力学和空穴跳跃如何控制远程电子转移速率。血红素辅因子被锌卟啉取代将使得氧化还原化学的光活化成为可能。 光谱速率测量是在CcP和Cc之间的一组结晶复合物中进行的，所述结晶复合物显示一系列缔合状态和反应性，设置氧化还原中心环境并固定分子取向。X射线衍射研究将直接关联结构与反应性。通过诱变，小分子互补，交联，温度变化和溶剂替代的研究，影响跳跃反应和蛋白质/溶剂动力学的参数将系统地探讨，所有的背景下，单晶。实验将通过计算研究进行指导和协调，该研究评估供体和受体位点之间的电子耦合作为构象状态和溶剂结构的函数。拟议的工作将揭示具体的参数，如桥结构，构象，氧化还原电位和跳跃位点环境影响远程ET在异构系统中类似于那些综合访问的设备开发。将通过向公共数据库提交数据和开发新的基于网络的工具来促进研究结果的传播，这些工具可以很容易地使电子供体/受体相互作用的结构/功能关系可视化。拟议的研究将培养生物，物理和无机化学的本科生和研究生，并与这些领域的研究人员正式教学工作良好的接口。

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports Professor Brian R. Crane at Cornell University to study long-range electron transfer between cytochrome c peroxidase (CcP) and cytochrome c (Cc) to ascertain how molecular associations, conformational dynamics, and hole hopping control long-range electron transfer rates. Substitution of heme cofactors by Zn-porphyrins will enable photo-activation of redox chemistry. Spectroscopic rate measurements are to be carried out in a set of crystalline complexes between CcP and Cc that display a range of association states and reactivities, set redox center environment and fix molecular orientation. X-ray diffraction studies will directly correlate structure with reactivity. Through mutagenesis, small-molecule complementation, cross-linking, temperature variation, and solvent substitution studies, parameters affecting hopping reactions and protein/solvent dynamics will be systematically probed, all in the context of single crystals. Experiments will be guided and reconciled by computational studies that assess electronic coupling between donor and acceptor sites as a function of conformational state and solvent structure. The proposed work will reveal how specific parameters, such as bridge structure, conformation, redox potentials and hopping site environment affect long-range ET in heterogeneous systems similar to those synthetically accessible for device development. Dissemination of findings will be facilitated by submission of data to public databases and the development of new web-based tools that readily allow the visualization of structure/function relationships for electron donor/acceptor interactions. The proposed research will train undergraduate and graduate students in bio-, physical- and inorganic chemistry and interface well with the investigators formal teaching efforts in these areas.