Electron transfer and oxidase activities in reconstituted hemoproteins with chemically modified cofactors

Abstract

Protoheme IX is a typical iron porphyrin cofactor, showing a variety of reactivities in many hemoproteins under the reaction environments provided by protein matrices. Chemical modification of the protoheme cofactor is expected to be a versatile strategy to design hemoproteins possessing unique functions. This review focuses on the conversion of a hemoprotein, mainly myoglobin (an oxygen-storage hemoprotein), into a protein having different functions from the original ones by replacement of the protoheme cofactor with synthetic cofactors. The myoglobin having anionic patches pended to the heme propionates effectively binds electron-accepting proteins or small cationic organic molecules on the protein surface, resulting in enhanced efficiency of the photoinduced electron transfers from the myoglobin to these electron acceptors. Furthermore, the peroxidase and peroxygenase activities are also enhanced due to the facile substrate accesses. The attachment of the chemically active moiety such as flavin at the heme terminal is also important to give P450-like function to the native myoglobin. The employment of a structural isomer of porphyrin as an artificial cofactor gives rise to remarkably high dioxygen affinity and peroxidase activity in myoglobin, and allows us to easily detect high-valent species of the porphyrin isomer in HRP. These examples provide a clear insight into hemoprotein modifications based on synthetic chemistry as well as genetic amino acid mutations.