PUTTING THE OH WHERE IT BELONGS

Abstract

ONLY A HANDFUL OF HEME proteins-for example, the medically important family of cytochrome P450 enzymes that metabolize drugs in the body-are capable of attaching hydroxyl groups to inert hydrocarbon substrates. A new X-ray absorption study of a model member of this protein class hints at what allows these enzymes to create reactive iron intermediates that can perform this demanding chemistry without destroying themselves. The active sites of cytochrome P450s contain a heme cofactor whose iron center is coordinated to the protein via a cysteine thiolate. During catalysis, these enzymes are thought to use dioxygen to generate an Fe(IV) = O radical species. This highly reactive ferryl radical species is thought to abstract hydrogen from the hydrocarbon substrate, forming a protonated ferryl that then hydroxylates the substrate. Somehow, this highly reactive ferryl radical species performs hydroxylations without oxidizing the surrounding enzyme. That's a remarkable feat, says Michael T. Green, an assistant ...