The role of residue M305 in Mammalian Cytochrome P450 2S1

Cytochrome P450 (CYP) is an essential enzyme present in all living organisms and is in charge of breaking down xenobiotics, metabolizing drugs, and takes part in steroid and vitamin synthesis. Cytochrome P450 2S1 (CYP2S1) is an unusual cytochrome because it only catalyzes the reduction of substrates under low concentrations of oxygen and has not conclusively shown to oxidize substrates. It is important because it is overexpressed in oxygen-deficient areas such as cancerous areas related to colorectal, metastatic ovarian, and carcinomas. CYP2S1 is being investigated as a prodrug target for cancer therapies. Prodrugs are inactive (nontoxic) until they become activated (toxic) by an enzyme such as CYP2S1. CYP2S1 has been shown to breakdown and reduce anticancer prodrug, AQ4N. However, the basic biochemistry of CYP2S1 and why this enzyme’s chemistry is different from other CYPs has not been investigated. Our hypothesis is M305 in CYP2S1 is responsible for preventing oxidation of substrates. Current research involves mutants to a model enzyme to determine the importance and role of M305 in the CYP2S1 structure.