Nitric oxide reduction by non-heme iron systems (FprA)

Nitric oxide is ubiquitous in living organisms and serves roles ranging from signal transduction to nitrate-based respiration. Nitric oxide can also be toxic. A novel class of bacterial proteins, FprA (type A flavoproteins, and their congeners flavorubredoxins), has recently been described, which catalyzes the detoxifying reduction of nitric oxide (NO) to nitrous oxide (N₂O):

2e^- + NO + 2H⁺ --> N₂O + H₂O (nitric oxide reductase).

FprAs feature a histidine and carboxylate-ligated diiron active site, similar to those in proteins known to perform dioxygen activation via O-O bond cleavage. We have been engaged in computational as well as experimental efforts to identify the catalytic mechanism, proposing that enzymatic nitric oxide reduction proceeds via a “super-reduced” Fe(II)-NO^- intermediate. Depicted below is the structure of FprA, as well as two alternative mechanisms for NO reduction.