An overview of the factors playing a role in cytochrome P450 monooxygenase and ferredoxin interactions

Abstract

Cytochrome P450 monooxygenases (CYPs/P450s) are heme-thiolate proteins that are ubiquitously present in organisms, including non-living entities such as viruses. With the exception of self-sufficient P450s, all other P450 enzymes need electrons to perform their enzymatic activity and these electrons are supplied by P450 redox proteins. Different types of P450 redox proteins can be found in organisms and are classified into different classes. Bacterial P450s (class I) receive electrons from ferredoxins which are iron-sulfur cluster proteins. The presence of more than one copy and different types of ferredoxins within a bacterial species poses fundamental questions about the selectivity of P450s and ferredoxins in relation to each other. Apart from transferring electrons, ferredoxins have also been found to modulate P450 functions. Achieving an understanding of the interaction between ferredoxins and P450s is required to harness their biotechnological potential for designing a universal electron transfer protein. A brief overview of factors playing a role in ferredoxin and P450 interactions is presented in this review article.

Keywords: Cytochrome P450 monooxygenase; Evolution; Ferredoxins; Heme; Interactions; Iron-sulfur cluster; Redox potentials.

Fig. 1

Structural analysis of the CYP11A1 (green) and adrenodoxin (yellow) binding interface (Sevrioukova et al. 1999). The proximal site of CYP11A1 is interacting with the loop surrounding the adrenodoxin (2Fe–2S) cluster. Hydrogen bonds and water (represented with small red spheres)-mediated hydrogen bonds between amino acids are also shown