Abstract
Copper-zinc superoxide dismutase (CuZnSOD) is one of a class of enzymes known to be excellent catalysts of the disproportionation of superoxide (2 O -2 + 2 H+ → O2 + H2O2). An unusual aspect of the structure of this enzyme is the occurrence of a bridging imidazolate ligand, which holds the copper and zinc ions in each subunit 6.3 Å apart. The mechanism of CuZnSOD-catalyzed superoxide disproportionation is understood in broad outline, but only relatively recently has it been possible to address several important aspects of the structure-function relationships in this enzyme. Of particular interest are the pH independence of both the spectroscopic and catalytic properties of this enzyme over a wide range of pH and the function of the zinc-imidazolate ligand to the copper in the catalytic mechanism. Recently, there have been several intriguing results concerning the physiological role played by CuZnSOD in vivo. There is a growing body of evidence indicating that oxidative damage in mammalian cells is associated with aging, carcinogenesis, and induction of other serious disease states and that toxic metabolites derived from the metabolism of O2 may be responsible for such damage. Superoxide dismutases have been proposed to act as antioxidant enzymes by lowering the steady state concentration of superoxide in vivo. Mutations in this enzyme have also been reported to be associated with the familial form of amyotrophic lateral sclerosis (ALS), frequently termed Lou Gehrig’s Disease, but the mechanism by which these mutations cause the disease is as yet unknown.
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Valentine, J.S., Ellerby, L.M., Graden, J.A., Nishida, C.R., Gralla, E.B. (1995). Copper-Zinc Superoxide Dismutase: Mechanistic and Biological Studies. In: Kessissoglou, D.P. (eds) Bioinorganic Chemistry. NATO ASI Series, vol 459. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-0255-1_8
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