Intermolecular Interactions in Cytochrome P450 Systems

Dear Colleagues,

The central role cytochrome P450 enzymes play in human drug metabolism makes them a major subject for studies of drug disposition, adverse drug effects, and drug–drug interactions. However, these enzymes are not functional alone but rather constitute a part of the membrane-bound multienzyme system of microsomal monooxygenase (MMO). The major components of MMO are multiple cytochrome P450 species, NADPH-P450 reductase (CPR), and cytochrome b₅. The presence of multiple cytochrome P450 species in the same membrane makes the limiting concentration of CPR of remarkable functional importance. Additionally, even though the system consisting of P450 and CPR is fully functional, the complete MMO system also involves cytochrome b₅, which exerts an allosteric effect and may also serve as an alternative source of electrons for P450 catalysis. Furthermore, due to physical interactions between multiple P450 species and the formation of their mixed oligomers, the composition of the P450 pool affects the functional properties of the system in a very complex, hard-to-predict manner. However, due to limited knowledge of the mechanisms of intermolecular interactions in MMO, our understanding of the mechanisms of functional integration in the cytochrome P450 ensemble remains essentially incomplete.

We are pleased to invite you to contribute to the Special Issue of MDPI Biology devoted to the mechanisms of  intermolecular interactions in cytochrome P450 systems. This Special Issue focuses on recent advances in this area and current trends in understanding the functioning of the microsomal cytochrome P450 ensemble as a multienzyme system. We welcome research articles and review papers devoted to any kind of intermolecular interactions in membranous cytochrome P450 monooxygenases, including (but not limited to) the interactions of cytochromes P450 with their redox partners, other drug-metabolizing enzymes (e.g., UGTs) and allosteric modulators (e.g., cytochrome b₅ and PGRMC2), homo- and heterooligomerization of cytochromes P450, interactions of CPR with electron acceptors other than cytochromes P450 (e.g., heme oxygenases), and protein-lipid interactions of MMO proteins. We believe this Special Issue will provide essential new information for taking a step forward to elucidating the principles of organization of the microsomal cytochrome P450 ensemble as an integrated system. We look forward to receiving your contributions.

Prof. Dr. Dmitri Davydov
Prof. Dr. John Hackett
Guest Editors

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