What determines the selectivity of arginine dihydroxylation by the nonheme iron enzymeOrfP?

The nonheme iron enzyme OrfP reacts with L-Arg selectively to form the three R ,4 R -dihydroxyarginine product, which in mammals can inhibit the nitric oxide synthase enzymes involved in blood pressure administration. To know the mechanisms of dioxygen activation of L-Arg by OrfP and the way in which it permits two sequential oxidation cycles on the equivalent substrate, we carried out a density sensible precept analysis on an enormous energetic website online cluster model. We current that substrate binding and positioning inside the energetic website online guides a extraordinarily selective response by the use of C 3 -H hydrogen atom abstraction.

This happens even if the C 3 -H and C 4 -H bond strengths of L-Arg are very comparable. Digital variations inside the two hydrogen atom abstraction pathways drive the response with an preliminary C 3 -H activation to a low-energy 5 s-pathway, whereas substrate positioning destabilizes the C 4 -H abstraction and sends it over the higher-lying 5 p-pathway. We current that substrate and monohydroxylated merchandise are strongly sure inside the substrate binding pocket and subsequently product launch is hard and consequently its lifetime may be prolonged ample to set off a second oxygenation cycle.