? As a first step to designing complex oxidoreductases, this project will develop a de novo designed hydrogen oxidation catalyst. The goal will be to clarify and reproduce the action of [NiFe]-hydrogenases in a designed peptide model system. First, a structured, designed, heine-binding protein or maquette will be redesigned to bind Ni and Ni-derived cofactors. Using structures of existing maquettes and analysis of hydrogenases, the Ni-binding maquette will be modified to incoporate aspects of hydrogenases: redox activity, hydrogen access, binding, and cleavage, and proton removal. Motifs believed to play a role in hydrogenase mechanism will be individually studied in the maquette model via structure determination and spectroscopic techniques. Since investigation of the hydrogenase active site is always complicated by the presence of other redox active components in the enzme, creation of a hydrogenase maquette will contribute fundamental knowledge to understanding biological hydrogen oxidation. Second, derived design principles will be combined to create a Ni-based active site for the oxidation of hydrogen. The knowledge gained in this study will become the building blocks for designing novel, de novo oxidoreductases. ? ?
| Jones, Anne K; Lichtenstein, Bruce R; Dutta, Arnab et al. (2007) Synthetic hydrogenases: incorporation of an iron carbonyl thiolate into a designed peptide. J Am Chem Soc 129:14844-5 |
