Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown (C.L. Borders, Jr. et al., (1989) Archives of Biochemistry and Biophysics, 268, 74-80) that the iron-containing (FeSOD) and manganese-containing (MnSOD) superoxide dismutases from Escherichia coli are extensively (greater than 98%) inactivated by treatment with phenylglyoxal, an arginine-specific reagent. Examination of the published primary sequences of these two enzymes shows that Arg-189 is the only conserved arginine. This arginine is also conserved in the three additional FeSODs and seven of the eight additional MnSODs sequenced to date, with the only exception being the MnSOD from Saccharomyces cerevisiae, in which it is conservatively replaced by lysine. Treatment of S. cerevisiae MnSOD with phenylglyoxal under the same conditions used for the E. coli enzymes gives very little inactivation. However, treatment with low levels of 2,4,6-trinitrobenzenesulfonate (TNBS) and acetic anhydride, two lysine-selective reagents that cause a maximum of 65-80% inactivation of the E. coli SODs, gives complete inactivation of the yeast enzyme. Total inactivation of yeast MnSOD with TNBS correlates with the modification of approximately 5 lysines per subunit, whereas 6-7 lysines per subunit are acylated with acetic anhydride on complete inactivation. It appears that the positive charge contributed by residue 189, lysine in yeast MnSOD and arginine in all other SODs, may be critical for the catalytic activity of MnSODs and FeSODs.
 ...
PMID:The positive charge at position 189 is essential for the catalytic activity of iron- and manganese-containing superoxide dismutases. 207 Oct 34

Bacteroides fragilis, an obligate anaerobe, synthesizes an azide-inhibitable iron-containing superoxide dismutase when grown in complex medium. Cells grown anaerobically in complex media containing desferrioxamine (Desferal, Ciba-Geigy) and graded concentrations of Mn synthesize the azide-resistant manganese-containing SOD. The fraction of MnSOD activity in dialyzed cell extracts increased progressively as the Mn concentration in the medium increased. The fraction of MnSOD activity also increased in extracts of cells grown in the medium with 1 mM Mn but with graded concentrations of desferrioxamine (0-10 micromolar). The SOD activity in the cells grown under the various conditions varied but not in a causal relationship with either Mn or desferrioxamine concentration. Electrophoresis revealed that the SOD activity in cells grown in the absence or presence of 1 mM Mn migrated with the same relative mobility and exhibited identical activity patterns when examined separately or as a mixture. These data are consistent with substitution of Mn for Fe in the B. fragilis apoprotein under anaerobic conditions and support the model of a single protein binding either Fe or Mn.
 ...
PMID:In vivo metal substitution in Bacteroides fragilis superoxide dismutase. 207 Oct 36

Escherichia coli growing anaerobically respond to NO3- with a approximately 3-fold induction of active FeSOD and a approximately 5.5-fold induction of an inactive, but activatable form of MnSOD (pro-MnSOD). Paraquat, which mediates anaerobic electron flow to NO3-, increased the induction of pro-MnSOD to approximately 2.5-fold. Strains with defects in the SOD genes or which lacked nitrate reductase activity failed to accumulate active or pro-forms of SODs in response to NO3- +/- PQ++. Diamide caused anaerobic induction of active MnSOD and this effect was also observed in a glutathione-negative strain. These inductions required de novo synthesis of protein, even when cell content of pro-MnSOD had been elevated by exposure to NO3- +/- PQ++ prior to addition of diamide. These results indicate that oxidation of a cell component increases biosynthesis of the SOD gene product and this postulated oxidation can be caused by terminal electron acceptors, such as dioxygen or NO3-. In addition, it appears that insertion of the correct metal can be rate-limiting, leading to competition by other metals and to the accumulation of inactive, incorrectly substituted pro-forms. Metal insertion may be dependent upon the valence of the metal, which may be influenced, in turn, by the redox status of the cells. Diamide and redox active agents such as ferricyanide may thus allow anaerobic production of active MnSOD by favoring the production of a complexed form of Mn(III) which can compete favorably with other metal cations for the active site of nascent MnSOD.
 ...
PMID:Anaerobic inductions of active forms of superoxide dismutases in Escherichia coli. 207 Oct 46

The 2.9 A resolution structure of iron superoxide dismutase (FeSOD) (EC 1.15.1.1) from Pseudomonas ovalis complexed with the inhibitor azide was solved. Comparison of this structure with free enzyme shows that the inhibitor is bound at the open coordination position of the iron, with a bond length of 2.0 A. The metal moves by 0.4 A into the trigonal plane to produce an orthogonal geometry at the iron. Binding of the inhibitor also causes a movement of the axial ligand (histidine 26) away from the metal, a lengthening of the iron-histidine bond, and a rotation of the histidine 74 ring. The inhibitor possesses contacts in the binding pocket with a pair of conserved tryptophan residues and with the side chains of tyrosine 34 and glutamine 70. This glutamine is conserved between all FeSODs, but is absent in MnSOD. Comparisons with MnSOD show that a different glutamine which possesses the same interactions in the active site as Gln70 in FeSOD is conserved at position 154 in the overall SOD sequence, implying that while manganese and FeSODs are structural homologues in a global sense, their functional and evolutionary relationship is that of second-site mutation revertants.
 ...
PMID:The structure of iron superoxide dismutase from Pseudomonas ovalis complexed with the inhibitor azide. 207 85

Superoxide dismutase (SOD) activity in hepatocellular carcinoma (HCC) tissue was studied. It was observed that activities of total SOD, Cu, Zn-SOD and Mn-SOD in HCC tissue were lower than those in normal liver tissues respectively (P less than 0.001 & 0.01 less than P less than 0.05). SOD activity in poorly differentiated HCC tissue was lower than that in well differentiated HCC tissue. Contents of copper, zinc and manganese in HCC tissues were lower than those in normal liver tissues respectively (P less than 0.001 & P less than 0.01). This study suggests that decreased content of copper, zinc and manganese may be one of the factors that lead to impairment of SOD activity. The characteristic of lower SOD activity in HCC tissue and poorly differentiated HCC tissue may be a negative regulation to limitless proliferation and poor differentiation of liver cancer cells.
 ...
PMID:[Superoxide dismutase activity in tissues from 19 cases of hepatocellular carcinoma]. 216 38

The ferric uptake regulation (fur) gene product participates in regulating expression of the manganese- and iron-containing superoxide dismutase genes of Escherichia coli. Examination of beta-galactosidase activity coded from a chromosomal phi(sodA'-'lacZ) fusion suggests that metallated Fur protein acts as a transcriptional repressor of sodA (manganese superoxide dismutase [MnSOD]). Gel retardation assays demonstrate high-affinity binding of pure, Mn2(+)-Fur protein to DNA fragments containing the sodA promoter. These data and the presence of an iron box sequence in its promoter strongly suggest that sodA is part of the iron uptake regulon. An sodB'-'lacZ fusion gene borne on either a low- or high-copy plasmid yielded approximately two- to threefold more beta-galactosidase activity in Fur+ compared with Fur- cells; the levels of activity depended only weakly on the growth phase and did not change during an extended stationary phase. Measurement of FeSOD activity in logarithmic growth phase and in overnight cultures of sodA and fur sodA backgrounds revealed that almost no FeSOD activity was expressed in Fur- strains, whereas wild-type levels were expressed in Fur+ cells. Fur+ and Fur- cells bearing the multicopy plasmid pHS1-4 (sodB+) expressed approximately sevenfold less FeSOD activity in the fur background, and staining of nondenaturing electrophoretic gels indicates that synthesis of FeSOD protein was greatly reduced in Fur- cells. Gel retardation assays show that Mn2(+)-Fur had a significantly higher affinity for the promoter fragment of sodB compared with that of random DNA sequences but significantly lower than for the promoter fragment of sodA. These observations suggest that the apparent positive regulation of sodB does not result exclusively from a direct interaction of holo (metallated) Fur itself with the sodB promoter. Nevertheless, the sodB gene also appears to be part of the iron uptake regulon but not in the classical manner of Fe-dependent repression.
 ...
PMID:Control of Escherichia coli superoxide dismutase (sodA and sodB) genes by the ferric uptake regulation (fur) locus. 218 Sep 12

Superoxide dismutase (SOD) molecules occur in all cells exposed to an oxygen-containing environment, including retinal pigment epithelial (RPE) cells. Previous studies of nonhuman RPE have either probed specifically for copper-zinc-containing SOD (CuZn-SOD) or have not distinguished between CuZn-SOD and the SOD molecule that contains manganese (Mn-SOD). The authors used specific enzymatic assays and immunologic probes, both in vivo and in vitro, to show that human RPE cells contain both CuZn-SOD and Mn-SOD. The CuZn-SOD had a diffuse cytosolic distribution, whereas the Mn form was located primarily in the mitochondria. The role of SODs in protecting the chorioretinal complex against oxidative damage and with regard to aging processes is not well understood and warrants further investigation, and the two cellular forms of SOD should be considered in future studies.
 ...
PMID:Human retinal pigment epithelium contains two distinct species of superoxide dismutase. 226 90

Three isozymes of superoxide dismutase (SOD) have been identified and characterized. The iron and manganese isozymes (Fe-SOD and Mn-SOD, respectively) show extensive primary sequence and structural homology, suggesting a common evolutionary ancestor. In contrast, the copper/zinc isozyme (CuZn-SOD) shows no homology with Fe-SOD or Mn-SOD, suggesting an independent origin for this enzyme. The three isozymes are unequally distributed throughout the biological kingdoms and are located in different subcellular compartments. Obligate anaerobes and aerobic diazotrophs contain Fe-SOD exclusively. Facultative aerobes contain either Fe-SOD or Mn-SOD or both. Fe-SOD is found in the cytosol of cyanobacteria while the thylakoid membranes of these organisms contain a tightly bound Mn-SOD. Similarly, most eukaryotic algae contain Fe-SOD in the chloroplast stroma and Mn-SOD bound to the thylakoids. Most higher plants contain a cytosol-specific and a chloroplast-specific CuZn-SOD, and possibly a thylakoid-bound Mn-SOD as well. Plants also contain Mn-SOD in their mitochondria. Likewise, animals and fungi contain a cytosolic CuZn-SOD and a mitochondrial Mn-SOD. The Mn-SOD found in the mitochondria of eukaryotes shows strong homology to the prokaryotic form of the enzyme. Taken together, the phylogenetic distribution and subcellular localization of the SOD isozymes provide strong support for the hypothesis that the chloroplasts and mitochondria of eukaryotic cells arose from prokaryotic endosymbionts.
 ...
PMID:Phylogenetic distribution of superoxide dismutase supports an endosymbiotic origin for chloroplasts and mitochondria. 226 71

The manganese-containing (MnSOD) and iron-containing (FeSOD) superoxide dismutases from Escherichia coli are extensively (greater than 95%) inactivated by treatment with phenylglyoxal. The relatively high concentrations of phenylglyoxal and high pH required for optimal inactivation suggest that inactivation may be due to modification of an arginine with a "normal" elevated pKa, i.e., one not in an active site cavity where the pKa is likely to be lowered because of lower solvent accessibility and decreased polarity of the local environment. Treatment of either enzyme with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, 2-hydroxy-5-nitrobenzyl bromide, m-chloroperoxybenzoate, or tetranitromethane causes no inactivation, while 2,4,6-trinitrobenzenesulfonate, N-acetylimidazole, or diethyl pyrocarbonate cause 55-75% inactivation of each enzyme. Failure of hydroxylamine to reverse inactivation by the latter two suggests that in each instance loss of activity is due to lysine modification. The previously reported inactivation of FeSOD by H2O2 was further investigated, and no evidence was found for an affinity mechanism, i.e., a reversible binding of peroxide that precedes inactivation.
 ...
PMID:Chemical modification of iron- and manganese-containing superoxide dismutases from Escherichia coli. 264 90

The genome of Escherichia coli codes for two superoxide dismutases that may contain either iron (FeSOD) or manganese (MnSOD) at the active site. The crystal structures of MnSODs from two bacterial sources (but not E. coli) have been completed, and structural comparisons with the crystal structure of the FeSOD from either E. coli or Pseudomonas ovalis have been made. Despite the low degree (less than 50%) of sequence homology between the E. coli enzymes, the two proteins are suggested to be structurally homologous. Nonetheless, these enzymes exhibit absolute metal cofactor specificity in conferring enzymatic activity to the inactive apoenzyme. This observation is surprising considering the identity of the active site ligands and the similarities in their geometry and surrounding environment. Using analytical ultracentrifugation, we have determined that the solution properties of these two proteins are different. Thus dialysis of FeSOD but not of MnSOD against phosphate buffer in the presence or absence of EDTA caused dissociation of the homodimer. This dissociation appeared to be related to the loss of iron from native FeSOD. Thus, apoFeSOD but not apoMnSOD existed predominantly as a monomer at protein concentrations below 150 micrograms/mL. ApoMnSOD showed no evidence for dissociation under these conditions. Fluorescence data suggest that the tryptophan environments for the two enzymes are also different. The results of these physical measurements lead us to propose that subtle differences, perhaps at the subunit contact faces, exist in the structures of these crystallographically similar proteins.
 ...
PMID:Differences between the manganese- and the iron-containing superoxide dismutases of Escherichia coli detected through sedimentation equilibrium, hydrodynamic, and spectroscopic studies. 266 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>