Electron transfer activation of chromopyrrolic acid by cytochrome P450 en route to the formation of an antitumor indolocarbazole derivative: Theory supports experiment

QM/MM calculations support experiment and show that StaP is a P450 that functions like a peroxidase: its active species is the one-electron-reduced Cpd II species with a radical on CPA, by analogy to cytochrome c peroxidase (CcP), and its reaction with the substrate proceeds by overall proton-coupled electron transfer (PCET), in analogy to the corresponding mechanism in horseradish peroxidase (HRP). The electron transfer is enabled by His₂₅₀, the presence of carboxylate groups in CPA, and by the H-bonding network that tunes the energetic of the process. Theory supports experiment but reveals some novel aspects of this unusual P450.