Conformational Dynamics and Hole-hopping in Metalloprotein Electron Transfer

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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.