What Determines the Selectivity of Arginine Dihydroxylation by the Nonheme Iron Enzyme OrfP

摘要: The nonheme iron enzyme OrfP reacts with l-Arg selectively to form the 3R,4R-dihydroxyarginine product, which in mammals can inhibit nitric oxide synthase enzymes involved blood pressure control. To understand mechanisms of dioxygen activation by and how it enables two sequential oxidation cycles on same substrate, we performed a density functional theory study large active site cluster model. We show that substrate binding positioning guides highly selective reaction through C3 -H hydrogen atom abstraction. This happens despite fact C4 bond strengths are very similar. Electronic differences abstraction pathways drive an initial low-energy 5 σ-pathway, while destabilizes sends over higher-lying π-pathway. monohydroxylated products strongly bound pocket hence product release is difficult consequently its lifetime will be long enough trigger second oxygenation cycle.