Title : Nitric Oxide Reductases: Molecular Evolution of Respiratory Enzymes and Global Environment


Nitric oxide reductase (NOR) is an integral membrane protein that is involved in microbial denitrification, a type of anaerobic respiration in which nitrate is reduced in a stepwise manner to dinitrogen (NO3-→ NO2-→ NO → N2O → N2). In this process, NOR catalyzes the reduction of nitric oxide (NO), which is generated as an intermediate product in this process, to nitrous oxide (N2O) using two protons and two electrons (2NO + 2H+ + 2e- → N2O + H2O) via N-N bond formation and N-O bond cleavage at a binuclear center consisting of heme and non-heme iron (FeB). The product of the NOR-catalyzed reaction, N2O, is a greenhouse gas that is 310 times more powerful than carbon dioxide, and is also an ozone depleting substance. Since the use of nitrogen-based fertilizer increases global N2O levels by stimulating the action of soil denitrifiers, NOR is an important topic of study with respect to the global environment. NOR also has clinical and pharmaceutical importance, as evidenced by the fact that some pathogens use NOR to detoxify cytotoxic NO produced by macrophages in immune system of a host. In addition, it has been believed that NOR shares the same ancestor proteins as cytochrome c oxidase (CCO), which is an aerobic respiratory enzyme catalyzing the O2 reduction (O2 + 4H+ + 4e- → 2H2O) at a binuclear center consisting of heme and copper (CuB). Recently, we succeeded in structural determination of NOR in the resting, reduced and ligand-bound states. In the lecture, I will show the molecular mechanism of the NO reduction catalyzed by NOR, which was proposed on the basis of their molecular structures, and discuss the structural and functional characteristics of NOR in relation to the molecular evolution of the respiratory enzymes by comparing them with those of CCO.