Heme iron centers in cytochrome P450: structure and catalytic activity

Abstract

Heme iron centers are found in a wide range of proteins where they play different roles for many crucial biological processes, including catalysis. Among heme-containing enzymes, the cytochromes P450 superfamily comprises members distributed in all domains of life where they participate in the metabolism of endogenous and exogenous compounds. These enzymes can perform a series of oxidative reactions on a broad range of chemically different substrates and for this reason are optimal candidates for biocatalytic purposes and, in general, technological applications. In this review, the general features of these enzymes will be discussed with particular emphasis on the structural insights obtained through X-ray crystallography to understand the key steps of their catalytic mechanism where oxygen is activated. Moreover, one of the finest multi-step reactions catalyzed by the cytochrome P450 aromatase, dealing with the conversion of androgens into estrogens, will be discussed in details. The X-ray structure of this enzyme, together with site-directed mutagenesis experiments has elucidated the role of key residues involved in substrate binding and catalysis. This last example shows how the function and structure in cytochromes P450 are closely inter-correlated to achieve a complex finely tuned catalytic mechanism. It is possible to exploit them for biotechnological applications, but careful attention must be paid in not altering their delicate structure on which their correct function strictly depends.