Dimeric copper-zinc superoxide dismutases

I. The Need for Superoxide Dismutase II. The Crystal Structures of Dimeric Copper-Zinc Superoxide Dismutases... 

CD spectroscopy has also provided valuable insight into the chemical stability and chemical denaturation of proteins. A recent study by Rumfeldt etal. examines the guanidinium-chloride induced denaturation of mutant copper-zinc superoxide dismutases (SODs). These mutant forms of the Cu, Zn-SOD enzyme are associated with toxic protein aggregation responsible for the pathology of amyotrophic lateral sclerosis. In this study, CD spectroscopy was used in conjunction with tryptophan fluorescence, enzyme activity, and sedimentation experiments to study the mechanism by which the mutated enzyme undergoes chemical denaturation. The authors found that the mutations in the enzyme structure increased the susceptibihty of the enzyme to form partially unfolded destabilized monomers, rather than the stable metaUated monomer intermediate or native metallated dimer. 

W.C. Stallings, T.B. Powers, K.A. Partridge, J.A. Fee, and M.L. Ludwig, Iron superoxide dismutase from Escherichia coli at 3.1. ANG. resolution a structure unlike that of copper/zinc protein at both monomer and dimer levels. Proc. Natl. Acad. Sci. U.SA. 80, 3884—3888 (1983). 

Superoxide dismutase enzymes are functional dimers of molecular weight (Mr) of approximately 32 kDa. The enzymes contain one copper ion and one zinc ion per subunit. Superoxide dismutase (SOD) metalloenzymes function to disproportionate the biologically harmful superoxide ion-radical according to the following reaction ... 

In bacteria, on the other hand, the similar dimeric superoxide dismutase contains two Mn(II) ions per mole and no copper or zinc (55). In contrast, the enzyme from higher plants (eukaryotes) appears to be the Zn-Cu dimeric protein. The enzyme from green peas has been isolated as a Zn-Cu protein with molecular weight 31,500 (53) (Table I). Of great interest is the evidence that the manganese superoxide dismutase is present in chicken liver mitochondria (58). 

Zinc usually binds to proteins via residues of cysteine and histidine. Sometimes, zinc is bound to residues of glutamate or aspartate. The zinc ion sometimes plays a catalytic role and sometimes a structural role. In the latter case, it helps maintain the three-dimensional structure or conformation of the protein. For example, carboxypeptidase A contains two atoms of zinc. One is required for catalytic activity and is boimd to cysteine and histidine. The other, which plays a structural role, is bound only to cysteine. Cytoplasmic superoxide dismutase is a dimer. It contains one atom of Cu " and one of Zn per subunit. The zinc is boimd via three residues of histidine and one residue of aspartate. It is buried deep within the enzyme and serves a structural role. The copper atom is bound via four residues of histidine. It resides close to the surface of the protein and participates in the chemistry of catalysis. 

The SDEL algorithm has also been applied to more complicated systems, such as the wild type human Cu, Zn superoxide dismutase (SOD) dimer. SOD is a 153-residue, homodimeric, anti-oxidant enzyme that dismutates superoxide ion to hydrogen peroxide and oxygen [87]. It is an eight-strand, flattened, beta-barrel protein with one copper and one zinc ion per monomer [88]. There are over 100... 

---