Aspects of the Structure, Function, and Applications of Superoxide Dismutas

Bannister, J.V.; Bannister, W.H.; Rotilio, Giuseppe

doi:10.3109/10409238709083738

Cited by 822 publications

(536 citation statements)

References 507 publications

Supporting

Mentioning

511

Contrasting

Unclassified

Order By: Relevance

“…SOD-1 is a protective enzyme responsible for maintaining lower levels of superoxide radicals within the cell (Fridovich, 1978;Bannister et al, 1987;Crapo et al, 1992). Previous studies have shown that down-regulation of SOD-1 activity induces apoptosis of neuronal cells (Troy and Shelanski, 1994) and that up-regulation of SOD-1 by shear stress is an important mechanism preserving the integrity of the endothelium after pro-apoptotic stimulation (Dimmeler et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Thiram inhibits angiogenesis and slows the development of experimental tumours in mice

Marikovsky

2002

Br J Cancer

View full text Add to dashboard Cite

Thiram-tetramethylthiuram disulphide -a chelator of heavy metals, inhibited DNA synthesis and induced apoptosis in cultured bovine capillary endothelial cells. Bovine capillary endothelial cells were 10 -60-fold more sensitive to thiram than other cell types. These effects were prevented by addition of antioxidants, indicating involvement of reactive oxygen species. Exogenously added Cu 2+ impeded specifically and almost completely the inhibitory effect of thiram for bovine capillary endothelial cells. Moreover, thiram had markedly inhibited human recombinant Cu/Zn superoxide dismutase enzymatic activity (85%) in vitro. Moreover, PC12-SOD cells with elevated Cu/Zn superoxide dismutase were less sensitive to thiram treatment than control cells. These data indicate that the effects of thiram are mediated by inhibition of Cu/Zn superoxide dismutase activity. Oral administration of thiram (13 -30 mg mouse 71 ), inhibited angiogenesis in CD1 nude mice. Tumour development is known to largely depend on angiogenesis. We found that oral administration of thiram (30 mg) to mice caused significant inhibition of C6 glioma tumour development (60%) and marked reduction (by 3 -5-fold) in metastatic growth of Lewis lung carcinoma. The data establish thiram as a potential inhibitor of angiogenesis and raise the possibility for its use as therapy in pathologies in which neovascularisation is involved, including neoplasia.

show abstract

Section: Discussionmentioning

confidence: 99%

Thiram inhibits angiogenesis and slows the development of experimental tumours in mice

Marikovsky

2002

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Each identical enzyme subunit contains 8 histidines: His 19 and 41 are not involved in metal binding, His 44, 46 and 118 are involved in the binding of Cu, His 69 and 78 coordinate to the Zn, and His 61 is a bridging ligand between the two metals in the oxidized enzyme. A great deal of spectroscopic evidence indicated that the copper-imidazolate bond of this bridge is broken with subsequent protonation of the latter group in the reduced Cu(I),Zn enzyme [2]. This event is relevant to the mechanism of action of the enzyme, which involves alternate reduction and oxidation of the enzyme by 02 to give Hz02 and 02 as products at a rate approaching diffusion-limited values [2].…”

Section: Introductionmentioning

confidence: 99%

“…A great deal of spectroscopic evidence indicated that the copper-imidazolate bond of this bridge is broken with subsequent protonation of the latter group in the reduced Cu(I),Zn enzyme [2]. This event is relevant to the mechanism of action of the enzyme, which involves alternate reduction and oxidation of the enzyme by 02 to give Hz02 and 02 as products at a rate approaching diffusion-limited values [2]. Therefore, knowledge of the structure of the active site of the reduced, or Cu(I), form of the enzyme is fundamental to the description of the catalytic mechanism; unfortunately the X-ray analysis of the Cu(I),Zn protein is not yet available.…”

Section: Introductionmentioning

confidence: 99%

Assignment of imidazole resonances from two‐dimensional proton NMR spectra of bovine Cu,Zn Superoxide dismutase

et al. 1990

Self Cite

View full text Add to dashboard Cite

Two-dimensional iH-NMR spectra were carried out on bovine Cu(I),Zn superoxide dismutase. The ring protons of the single tyrosine and of the 4 phenylalanines were identitled from COSY spectra. From NOESY spectra all imidaxole C-resonances could be specifically assigned to each of the 8 histidines using the crystal coordinates of the Cu(II),Zn enzyme. Since 6 hi&dines are involved in the structure of the active site, this result implies nearly identical active site conformations for the two oxidation states of the catalytic cycle of this enzyme, in line with its ditfusion-limited rate.

show abstract

“…The reported roles of superoxide radicals in ischemiareperfusion injury, inflammatory response, chemical toxicity, and radiation damage have led to the suggestion that superoxide dismutases be employed as therapeutic agents (Bannister et al, 1987;McCord, 1988;Parizada et al, 1990;Gorecki et al, 1991), and have prompted the cloning and expression of human manganese superoxide dismutase (Beck et al, 1988). Human MnSOD is an enzyme with a subunit molecular weight of 22,200 daltons, consisting of 198 amino acids of known sequence (Barra et al, 1984;Beck et al, 1987).…”

mentioning

confidence: 99%

Comparison of the crystal structures of genetically engineered human manganese superoxide dismutase and manganese superoxide dismutase from thermus thermophilus: Differences in dimer–dimer interaction

et al. 1993

View full text Add to dashboard Cite

The three‐dimensional X‐ray structure of a recombinant human mitochondrial manganese superoxide dismutase (MnSOD) (chain length 198 residues) was determined by the method of molecular replacement using the related structure of MnSOD from Thermus thermophilus as a search model. This tetrameric human MnSOD crystallizes in space group P21212 with a dimer in the asymmetric unit (Wagner, U.G., Werber, M.M., Beck, Y., Hartman, J.R., Frolow, F., & Sussman, J.L., 1989, J. Mol. Biol. 206, 787–788). Refinement of the protein structure (3, 148 atoms with Mn and no solvents), with restraints maintaining noncrystallographic symmetry, converged at an R‐factor of 0.207 using all data from 8.0 to 3.2 Å resolution and group thermal parameters. The monomer–monomer interactions typical of bacterial Fe‐ and Mn‐containing SODs are retained in the human enzyme, but the dimer–dimer interactions that form the tetramer are very different from those found in the structure of MnSOD from T. thermophilus. In human MnSOD one of the dimers is rotated by 84° relative to its equivalent in the thermophile enzyme. As a result the monomers are arranged in an approximately tetrahedral array, the dimer–dimer packing is more intimate than observed in the bacterial MnSOD from T. thermophilus, and the dimers interdigitate. The metal—ligand interactions, determined by refinement and verified by computation of omit maps, are identical to those observed in T. thermophilus MnSOD.

show abstract

Aspects of the Structure, Function, and Applications of Superoxide Dismutas

Cited by 822 publications

References 507 publications

Thiram inhibits angiogenesis and slows the development of experimental tumours in mice

Thiram inhibits angiogenesis and slows the development of experimental tumours in mice

Assignment of imidazole resonances from two‐dimensional proton NMR spectra of bovine Cu,Zn Superoxide dismutase

Comparison of the crystal structures of genetically engineered human manganese superoxide dismutase and manganese superoxide dismutase from thermus thermophilus: Differences in dimer–dimer interaction

Contact Info

Product

Resources

About