Superoxide dismutase characteristics

Fig. 20. An example of antiparallel /3 sheet, from Cu,Zn superoxide dismutase (residues 93-98,28-33, and 16-21). Arrows show the direction of the chain on each strand. Main chain bonds are shown solid and hydrogen bonds are dotted. In the pattern characteristic of antiparallel /8 sheet, pairs of closely spaced hydrogen bonds alternate with widely spaced ones. The direction of view is from the solvent, so drat side chains pointing up are predominantly hydrophilic and those pointing down are predominantly hydrophobic.

Iron-containing superoxide dismutases are present in many species of bacteria (Hassan and Fridovitch, 1978). These nonheme iron proteins have a characteristic set of EPR lines split about g = 4.2 in the ferric state, arising from the middle Kramers doublet of a rhombic high-spin site. Ferrous iron superoxide dismutase forms an S = I complex with NO that resembles the lipoxygenase-NO adduct by EPR criteria (I. Fridovich, T. Kirby, and J. C. Salerno, (1978) unpublished observations). 

Zepp, R. A., Chelack, W. S., Petkau, A. Bovine superoxide dismutase preparations Comparison of their biochemical and biological characteristics. In Chemical and Biochemical Aspects of Superoxide and Superoxide Dismutase (Bannister, J. V., Hill, H. A. O., eds.). New York-Amsterdam-Oxford, Elsevier/North-Holland, 1980, pp. 201-211 Rigo, A. et al. Biochem. J. 161, 27 (1977)... 

The antibody-dependent lysis of tumor cells by PMNs exhibited some of the characteristics of damage mediated by products of the burst in the presence of tumor cells there was increased consumption of O2, increased formation of O and activation of the hexose monosphosphate shunt However, although a reduction in the concentration of O2 in the medium inhibited lysis neither catalase nor superoxide dismutase inhibited. The lack of effect on these enzymes was attributed to their inability to interpose themselves between the plasma membranes of the PMN and its target. Similar conclusions were reached by Clark, and Klebanoff whose data incriminated the products of the burst by the reduced killing of tumor cells by PMNs from patients with chronic granulomatous disease. Myeloperoxidase, however, appeared not to he required since neither azide or cyanide inhibited and killing by PMNs from patients with inherited deficiency of myeloperoxidase was normal. 

The three-dimensional structure of human extracellular superoxide dismutase (EC-SOD) is unknown. Studies of structure-function relationships have been severely limited by its poor production in mammalian cell lines and failure to be expressed in prokaryotic and yeast systems. In contrast, extra- and intracellular Cu- and Zn-containing superoxide dismutases (CuZn-SOD) are expressed very well in E. coli and yeast. CuZn-SOD is homologous to a large interior fragment of EC-SOD, but lacks its extra N-terminal and C-terminal domains. Fusions of either the N-terminal domain of EC-SOD or both the N- and C-terminal domains of EC-SOD to CuZn-SOD resulted in a domain-swapped enzyme that expressed well and whose characteristics resemble EC-SOD (Stenlund and Tibell, 1999). 

While the stoichiometries of the Mn SOD enzymes appear to vary, the properties of the Mn-binding site do not. This is borne out in the electronic spectra of these proteins, which display a great degree of similarity despite the diversity of sources from which they have been isolated (Table II). This type of spectrum is distinctive for manganese in the trivalent oxidation state (3). The native enzymes are EPR silent, as might be anticipated if they contained Mn solely as the trivalent ion (S = 2) (1, 6,12,18-20, 24). However, when the enzymes are denatured, the characteristic six-line pattern of Mn(II) (I = 5/2) appears. Magnetic susceptibility studies with the E. coli SOD were consistent with the presence of a monomeric Mn(III) complex with a zero-field splitting of 1 to 2 cm-1 (4). The enzymes are additionally metal specific (however, see Refs. 36 and 37) metal reconstitution studies with E. coli and B. stearothermophilus revealed a strict requirement for Mn for superoxide dismutase activity (2, 22, 23). 

Autor AP, Frank L, Roberts RJ. Developmental characteristics of pulmonary superoxide dismutase Relationship to idiopathic respiratory distress syndrome. Pediatr Res 10 ( 976) 154-158. 

The exact mechanism responsible for the nephrotoxic effect of silicon remains to be elucidated although membrane damage possibly related to oxidant generation [89] or inhibition of superoxide dismutase activity [91] might be rational explanations. Based on reports on lung toxicity related to the chemical, morphological and surface characteristics of the various sihcon compounds, it is not known yet to which extent these exhibit direct toxic effects at the level of the kidney [90,92]. 

Phelan, A. M. and Lange, D. G. (1991) Ischemia-reperfusion-induced changes in membrane fluidity characteristics of brain capillary endothelial cells and its prevention by liposomal-incorporated superoxide dismutase. Biochim. Biophys. Acta 1067, 97-102. 

There it may attack the synovial fluid, destroying its capacity to lubricate the joint surfaces (7,8). Metal complexes have been shown to catalytically remove superoxide (9), and osmium containing deposits could perform a similar function. Osmium exhibits many of the characteristics believed necessary for these catalytic properties. The fact that the enzyme superoxide dismutase has been successfully used to treat arthritis in both animals (10) and humans (n,12) is further support for the suggestion. 

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