Superoxide Reductase

Abstract

Superoxide reductase (SOR) is a small bacterial metalloprotein, which is present in the cytoplasm of some anaerobic or microaerophilic microorganisms. SOR is involved in the detoxification of the superoxide radical and catalyzes its one‐electron reduction into hydrogen peroxide. Three different classes of SOR have been identified and structurally characterized. They all contain a similar active site, which consists of an unusual nonheme iron center, coordinated in a square‐pyramidal geometry to four nitrogens from four histidine side chains in the equatorial plane and the sulfur of one cysteine residue along the fifth axial position. In the reduced state, the sixth axial coordinating site of the iron is vacant, suggesting the most obvious site for initial binding of the superoxide substrate. The reaction mechanism of SOR has been studied by pulse radiolysis. SOR reacts specifically at a nearly diffusion‐controlled rate with O 2 •− , generating H 2 O 2 and the oxidized Fe 3+ active site. Reaction intermediates have been observed and proposed to be Fe 3+ ‐(hydro)peroxo species, resulting from the fast electron transfer from the ferrous iron to the superoxide anion and from protonation step. Formation of Fe 3+ ‐(hydro)peroxo intermediate species in the active site of SOR has been supported by resonance Raman spectroscopy and X‐ray structures of iron(III) peroxide species in the SOR from Desulfoarculus baarsii .

Hydrogen bonding to the cysteine ligand of superoxide reductase: acid–base control of the reaction intermediates

“…The second one, superoxide reductase (SOR), has been discovered more recently [5,6] and up to now has been only found in microorganisms [7][8][9][10]. SOD and SOR are structurally unrelated metalloproteins and carry out different reactions.…”

“…SOR catalyzes the one-electron reduction of O 2 •into H 2 O 2 (eq. 1), the electron being provided by cellular reductases or soluble electron transfer proteins [7][8][9][10]:…”

“…Although different classes of SOR have been described depending on the presence of an additional structural domain, which can bind a rubredoxin-like iron center (named center I), they all exhibit the same active site, named center II [7][8][9][10]. The SOR active site in its reduced form consists of an unusual non-heme Fe 2+ center in a [His 4 Cys 1 ] square pyramidal pentacoordination [11][12][13][14], which reacts at a nearly diffusion-controlled rate with O 2 - [15][16][17][18][19].…”

“…to be an essential feature for the reactivity of the enzyme with superoxide [7][8][9][10]. However, cysteine substitution to probe its function is not possible, since it would lead, most likely, to the formation of a demetallated SOR active site [21].…”