Superoxide Dismutases and Superoxide Reductases

The purpose of this Review is to describe, compare, and contrast the properties of the superoxide reductase and the four superoxide dismutase enzymes; to summarize what is known about their evolutionary pathways; and to analyze the properties of these enzymes in light of what is known of the inherent chemical reactivity of superoxide

Yuewei Sheng; Isabel A. Abreu; Diane E. Cabelli; Michael J. Maroney; Anne-Frances Miller; Miguel Teixeira; Joan Selverstone Valentine

2014

Scholarcy highlights

  • Superoxide, O2−, is formed in all living organisms that come in contact with air, and, depending upon its biological context, it may act as a signaling agent, a toxic species, or a harmless intermediate that decomposes spontaneously
  • Experiments showed that the E° of Fe is ∼0.3 V higher when Fe is bound in E. coli FeSOD protein than when it is bound in the E. coli Manganese superoxide dismutase protein, and the E° of mutans123 E. coli is ∼0.5 V higher when Mn is bound in the FeSOD protein than when it is bound in the MnSOD protein.74a,75a
  • The formation of the disulfide bond in SOD1 was monitored in live Escherichia coli and human cells using in-cell NMR.285a,c Expression of hSOD1 in human HEK293T cells without zinc or copper supplements resulted in two forms of disulfide-reduced SOD1, the apo form and the Zn-bound form.285a Zn2+ supplemented to growth media was taken up by hSOD1 expressed in E. coli and human cells, leading to the disulfide-reduced, Zn-bound protein.285a,c Coexpression of human copper chaperone for SOD1 with human SOD1 in zinc-supplemented media resulted in Cu-deficient, Zn-bound SOD1 with ∼50% oxidized disulfide bond, and complete disulfide formation was observed after the cells were incubated with Cu(II).285a These findings suggest that the disulfide oxidation of SOD1 by CCS can occur independently of copper insertion.285a
  • The fact that four evolutionarily unrelated metalloenzymes arose to protect organisms against O2− toxicity, that is, nickel-containing SODs, Fe/MnSODs, CuZnSOD, and superoxide reductase, provides excellent examples both of convergent evolution and of nature’s ingenuity. These efficient and robust systems allowed life to continue developing after the Great Oxidation
  • Event occurred on early Earth, by combating the products of noncontrolled and incomplete O2 reduction
  • There are some striking similarities in these four very different enzymes, which are certainly a consequence of the reactions catalyzed. Their reduction potentials all fall between the one-electron potentials reduction for of one-electron reduction of O2−
  • The reaction pathway involved in O2− disproportionation has been addressed using DFT to explore the potential energy surface, in inner-sphere processes.99a The preferred mechanism is shown in Figure 12 and features a reduced form of nickel-containing SODs that features a protonated Cys ligand and retains axial His imidazole coordination

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