Nickel-containing superoxide dismutases

Wuerges J, J-W Lee, Y-I Yim, H-S Yrm, S-O Kang, KD Carugo (2004) Crystal structure of nickel-containing superoxide dismutase reveals another type of active site. Proc Natl Acad Sci USA 101 8569-8574. 

Kim, I.K., Yim, Y.I., Kim, Y.M., Lee, J.W., Yim, H.S., Kang, S.O., 2003. CbiX-homologous protein (CbiXhp), a metal-binding protein, from Streptomyces seoulensis is involved in expression of nickel-containing superoxide dismutase. FEMS Microbiol. Lett. 228, 21—26. 

Nickel is found in thiolate/sulflde environment in the [NiFe]-hydrogenases and in CODH/ACS.33 In addition, either a mononuclear Ni-thiolate site or a dinuclear cysteine-S bridged structure are assumed plausible for the new class of Ni-containing superoxide dismutases, NiSOD (A).34 [NiFe]-hydrogenase catalyzes the two-electron redox chemistry of dihydrogen. Several crystal structures of [NiFe]-hydrogenases have demonstrated that the active site of the enzyme consists of a heterodinuclear Ni—Fe unit bound to thiolate sulfurs of cysteine residues with a Ni—Fe distance below 3 A (4) 35-39 This heterodinuclear active site has been the target of extensive model studies, which are summarized in Section 6.3.4.12.5. 

Lee JW, Roe JH and Kang SO (2002a) Nickel-containing superoocide dismutase. In Superoxide Dis-mutase, Vol. 349, pp. 90-101. Academic Press, Inc., San Diego. 

To diminish these threats, nature has created a family of metalloenzymes, the SODs. They catalyze the dismutation of superoxide to dioxygen and hydrogen peroxide (Eqs. (1) and (2)). They are differentiated by the redox-active metal copper (Cu/Zn SOD), manganese (MnSOD), iron (FeSOD), or nickel (NiSOD) superoxide dismutases and fall into three evolutionary families (Fig. 2) (10). The iron and manganese SODs are structurally similar and are found in prokaryotes and in the matrix of mitochondria (near the electron transport chain), respectively. Nickel containing SODs are known in some prokaryotes, whereas Cu/Zn are present in the cytosols of virtually all eukaryotic cells and have an independent evolutionary history. 

In contrast to the abundance of Fe-proteins, there are only six known nickel-containing enzymes hydrogenase, CO dehydrogenase (CODA), acetyl-CoA synthase (ACS), superoxide dismutase, urease, and S-methyl-CoM methylreductase. Among these enzymes, it exists in very diverse environments, including a dinickel site (urease), a Ni-Fe heterobinuclear site (hydrogenase), a Ni-Fe4S4 heterometallic... 

Superoxide dismutases may contain a range of metals Mn, Fe, or both Cu and Zn, and representatives of all these are found in prokaryotes. The nickel enzyme is noted later. 

Superoxide dismutase (SOD) catalyzes the disproportionation of superoxide to peroxide and oxygen according to equation (2). Four different types of SOD are known, containing either Cu and Zn see Copper Proteins with Type 2 Sites), Fe, Mn, or Ni see Nickel Enzymes Cofactors). The Fe and Mn containing SODs have very similar structures and can be further subdivided into metal-specific (i.e. functioning only when the correct metal is bound) and cambialistic (functioning with either Fe or Mn bound to the active site). 

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