Superoxide reductase: fact or fiction?

Abstract

It was recently proposed that anaerobic microorganisms contain a new pathway for detoxification of reactive oxygen species. This is centered around a novel mononuclear iron-containing enzyme, superoxide reductase (SOR), which catalyzes the reduction, rather than the dismutation, of superoxide to hydrogen peroxide. A surprisingly large amount of relevant data has accumulated in the two years or so since the proposal was made. Herein we address the questions: to what extent has the pathway been validated, and what fundamental issues have yet to be answered in considering the response of anaerobes to reactive oxygen species? The evidence for superoxide reduction by SOR is now overwhelming and comes from a variety of anaerobic and microaerophilic species. Moreover, the available spectroscopic and structural information provide a convincing case that the catalytic Fe site of SOR is structurally and electronically tuned to mediate superoxide reduction rather than oxidation. Kinetic analyses also support the original proposal of NAD(P)H, via rubredoxin and NAD(P)H:rubredoxin oxidoreductase, as the source of reductant. What is still to be determined is the fate of the peroxide generated by the SOR reaction. In particular, the role of otherwise well-characterized proteins like rubrerythrin, NADH peroxidase, and rubredoxin:oxygen oxidoreductase in "anaerobic" oxygen metabolism has yet to be established.

Rational Design of a Mononuclear Metal Site into the Archaeal Rieske-type Protein Scaffold

“…In light of the structural similarity of the biological Riesketype [2Fe-2S] clusters to the mononuclear iron center in Rd (17), which plays a central electron transfer function in the molecular oxygen-scavenging system in the hyperthermophiles (29,30), we replaced three residues (His-44, Lys-45, and His-64) in S. solfataricus ARF with cysteines and isoleucine (H44I/ K45C/H64C) to mimic the mononuclear iron site in the Rd from the hyperthermophile Pyrococcus furiosus (31) (Fig. 1).…”

An engineered two-iron superoxide reductase lacking the [Fe(SCys) 4 ] site retains its catalytic properties in vitro and in vivo

“…SORs have recently attracted a great deal of attention because of their novel activity and unique square-pyramidal ferrous [Fe(NHis) 4 (SCys)] active site (9)(10)(11)(12)(13)(14)(15)(16). Due at least in part to its high reduction potential [Ն200 mV vs. normal hydrogen electrode (NHE)], this ferrous site is remarkably stable to oxidation in air, yet it reacts with superoxide in an essentially diffusion-controlled fashion, as diagrammed in Fig.…”

Response of a strict anaerobe to oxygen: survival strategies in Desulfovibrio gigas

“…An iron superoxide dismutase and a catalase from D. gigas were recently purified and characterized in detail (Dos Santos et al, 2000). D. gigas and other strict anaerobes are equipped with alternative protection systems: neelaredoxin, the blue-coloured protein first isolated from D. gigas (Chen et al, 1994), present in all known genomes of anaerobic prokaryotes, has been identified as a scavenger of the superoxide anion radical (Silva et al, 2001b;Abreu et al, 2002;Adams et al, 2002). On the other hand, oxidative stress protection systems involving desulforedoxin (rubredoxin oxidoreductase) with superoxide reductase activity have been found in D. vulgaris (Lumppio et al, 2001).…”