Catalytically relevant electrostatic interactions of cytochrome P450c17 (CYP17A1) and cytochrome b5

Abstract

Background: Cytochrome b5 (b5) stimulates the 17,20-lyase activity of cytochrome P450c17 (CYP17A1). Results: A carboxylate group in b5 residues Glu-48/Glu-49 is required for 17,20-lyase activity, and cross-linked peptides Lys-88(CYP17A1)-Glu-61(b5) and Lys-347(CYP17A1R347K)Glu-42(b5) involve adjacent residues. Conclusion: These data support a molecular model of a CYP17A1-b5 complex. Significance: The CYP17A1-b5 interaction site might be a drug target to inhibit androgen synthesis.