Myoglobin Derivatives Reconstituted with Modified Metal Porphyrinoids as Structural and Functional Models of the Cytochrome P450 Enzymes
Reconstitution of hemoproteins with artificial heme analogues is an attractive strategy for modifying protein functions. In this chapter, two different reconstituted hemoproteins, cytochrome P450cam and myoglobin, are demonstrated. First, the role of the two heme–propionate side chains in cytochrome P450cam is discussed in the context of reconstituted P450cam with a one-legged heme, where one of the propionate side chains is replaced with a methyl group. The reconstituted cytochrome P450cam with the 7-methyl-7-despropionate heme indicates that the 7-propionate side chain plays an important role in the control of the process of expelling water molecules from the heme pocket out to the bulk solvent upon binding of a substrate molecule. Second, reconstituted myoglobins with artificial cofactors are reported models of cytochrome P450. Although native myoglobin does not have P450 activity, a reconstituted myoglobin with a flavin-attached heme and manganese porphycene, a constitutional isomer of porphyrin, have been found to promote the deformylation of 2-phenylpropionaldehyde and hydroxylation of inert alkanes, respectively. These results indicate that such reconstitutions of hemoproteins can provide important insights into understanding the structure/function relationships of hemoproteins and the generation of new biocatalysts.