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

The crystal structure of dimeric Fe(III) superoxide dismutase (SOD) from Escherichia coli (3006 protein atoms, 2 irons, and 281 solvents) has been refined to an R of 0.184 using all observed data between 40.0 and 1.85 A (34,879 reflections). Features of this structure are compared with the refined structure of MnSOD from Thermus thermophilus. The coordination geometry at the Fe site is distorted trigonal bipyramidal, with axial ligands His26 and solvent (proposed to be OH-), and in-plane ligands His73, Asp156, and His160. Reduction of crystals to the Fe(II) state does not result in significant changes in metal-ligand geometry (R = 0.188 for data between 40.0 and 1.80 A). The arrangement of iron ligands in Fe(II) and Fe(III)SOD closely matches the Mn coordination found in MnSOD from T. thermophilus [Ludwig, M.L., Metzger, A.L., Pattridge, K.A., & Stallings, W.C. (1991) J. Mol. Biol. 219, 335-358]. Structures of the Fe(III) azide (40.0-1.8 A, R = 0.186) and Mn(III) azide (20.0-1.8 A, R = 0.179) complexes, reported here, reveal azide bound as a sixth ligand with distorted octahedral geometry at the metal; the in-plane ligand-Fe-ligand and ligand-Mn-ligand angles change by 20-30 degrees to coordinate azide as a sixth ligand. However, the positions of the distal azide nitrogens are different in the FeSOD and MnSOD complexes. The geometries of the Fe(III), Fe(II), and Fe(III)-azide species suggest a reaction mechanism for superoxide dismutation in which the metal alternates between five- and six-coordination. A reaction scheme in which the ligated solvent acts as a proton acceptor in the first half-reaction [formation of Fe(II) and oxygen] is consistent with the pH dependence of the kinetic parameters and spectroscopic properties of Fe superoxide dismutase.
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PMID:Structure-function in Escherichia coli iron superoxide dismutase: comparisons with the manganese enzyme from Thermus thermophilus. 784 24

The X-ray structure of the tetrameric iron-dependent superoxide dismutase from Mycobacterium tuberculosis has been refined to an R-factor of 0.167 and a correlation coefficient of 0.954 at 2.0 A resolution. The crystals are monoclinic P2(1) and have four subunits related by strong non-crystallographic 222 (or D2) symmetry in the asymmetric unit. 198 of the 207 amino acids of each subunit are defined by the electron density which shows that they adopt the conserved fold of other iron- or manganese-dependent SODs. The structure can be divided into two domains, the N-terminal domain involving an extended region followed by two projecting antiparallel alpha-helices, and the C-terminal domain containing four more helical segments with a three-stranded antiparallel beta-sheet inserted sequentially between the fourth and fifth helices. The catalytic iron is co-ordinated by five ligands: three histidines (residues 28, 76 and 164), one aspartate (160) and a solvent molecule. The inferred positions of protons at the active site are consistent with the solvent ligand being a hydroxide ion. This ligand interacts with His145 in the Mycobacterium tuberculosis SOD. In the highly homologous Mycobacterium leprae Mn-SOD, the histidine is replaced by glutamine, this being the only significant residue difference within 10 A of the Fe3+. The nature of the amino acid at this position may influence the metal ion specificity of these enzymes. The subunits of the Mycobacterium tuberculosis SOD associate by polar contacts to form dimers, which closely resemble those of other dimeric or tetrameric Fe- or Mn-SODs. However, the dimer-dimer interactions within the tetramer are novel, being dominated by dimerisation of the 144 to 152 loop regions which connect the outer two beta-strands of the three-membered beta-sheet. This contrasts strongly with the other tetrameric Fe- or Mn-SODs where the dimer-dimer association is dominated by the projecting alpha alpha-turn in the N-terminal domain.
J Mol Biol 1995 Mar 03
PMID:X-ray structure analysis of the iron-dependent superoxide dismutase from Mycobacterium tuberculosis at 2.0 Angstroms resolution reveals novel dimer-dimer interactions. 787 74

During reperfusion of ischemic brain tissue, the production of reactive oxygen species initiates several modifications of the astroglial functional and ultrastructural integrity. During 24 h after ischemic treatment, modification of cellular superoxide free radical scavenging systems have been observed in primary culture of rat astroglial cell. Mitochondrial Mn superoxide dismutase activity (Mn-SOD) gradually decreases, whereas that of the cytosolic Cu,Zn form of the enzyme remains unaffected. We observed in parallel a significant decrease of glutamine synthetase (GS), an astrocyte specifically located enzyme. Addition of almitrine (dialylamine-4',6'-triazinyl 2')-1-(bis-parafluoro-benzydryl)-4-piperazine or dibucaine (a phospholipase A2 inhibitor) antagonizes the decrease of Mn-SOD activity, but does not affect modification of GS activity. Combined effects are observed by simultaneous addition of both drugs. Our data demonstrate that almitrine may increase the synthesis of some mitochondrial proteins, like Mn-SOD, and provide support for further study on the therapeutic potential of almitrine in ischemic astroglial cell injury.
Mol Chem Neuropathol 1993 Oct
PMID:Almitrine prevents some hypoxia-induced metabolic injury in rat astrocytes. 790 67

Antioxidant enzymes located in the bronchial epithelium can be expected to be important in protecting these cells against both endogenous and exogenous oxidants. In this study, human bronchial epithelial cells were isolated and cultured from specimens obtained from donors for lung transplantation. The levels and relative importance of different antioxidant enzymes were also assessed using an immortalized human bronchial epithelial cell line (BEAS 2B cells). Immunocytochemical studies showed a similar pattern of intracellular localization with the moderate degrees of labeling for Mn superoxide dismutase (SOD), CuZn SOD, and catalase in freshly isolated bronchial epithelial cells, bronchial epithelial cells in primary culture, and BEAS 2B cells. CuZn SOD and catalase decreased in labeling density whereas Mn SOD was unchanged when bronchial epithelial cells were placed in primary cultures. In contrast, Mn SOD and catalase were decreased in BEAS 2B cells compared with primary cultures. Although Mn SOD was low in BEAS 2B cells, it could be significantly induced by tumor necrosis factor treatment. Biochemical analysis showed remarkably similar catalase and glutathione reductase activities in primary cultured epithelial cells and BEAS 2B cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Nov
PMID:Primary and immortalized (BEAS 2B) human bronchial epithelial cells have significant antioxidative capacity in vitro. 794 85

MnSOD is an antioxidant enzyme whose decrease in activity appears involved in tumorigenesis. We had previously reported the production of a monoclonal antibody, named 35.8, against rat MnSOD. In the present paper we show that it recognizes human and mouse MnSODs, although with different detection limits. We also use the antibody for immunofluorescence studies and observed that the antibody yields a positive staining of a non-nuclear protein, in rat and human organs where high concentration of MnSOD activity have been reported, and a lack of staining in rat kidney where MnSOD activity is decreased. Two tumors, an experimental rat hepatocarcinoma and a human liver metastasis from a gastrointestinal adenocarcinoma, are found negative for immunostaining.
Biochem Mol Biol Int 1994 May
PMID:Monoclonal antibody 35.8 recognizes human, mouse and rat MnSODs in western blot and immunostaining. 808 Dec

A genomic clone encoding manganese-containing superoxide dismutase (SOD; EC 1.15.1.1) was isolated from a Hevea brasiliensis genomic library made in lambda phage EMBL3 by using a heterologous cDNA probe of MnSOD from Nicotiana plumbaginifolia. The nucleotide sequence of 4968 bp from the genomic clone was determined. Based on the putative translation initiation codon and stop codon, PCR primers were designed and utilized for cloning the full-length cDNA from total mRNA. Of the two distinct cDNAs of MnSOD isolated, MnSOD-A has a perfect match with exons of the nuclear gene, while MnSOD-B has a 90.2% homology and is 6 nucleotides longer than MnSOD-A in the putative transit peptide region. The nuclear gene comprises 6 exons and 5 introns, giving a total length of 3211 bp. The sequences of 1400 bp upstream of the initiation codon and 320 bp downstream of the stop codon were also determined. Southern analysis of genomic DNA from Hevea probed with a genomic fragment indicated there are at least two genes of MnSOD in Hevea. Northern blot analysis showed that MnSOD transcripts were present in all tissues examined (leaf, petiole, root, latex, callus) with young leaves showing the highest levels in intact plants. The transcript level in embryogenic callus was nearly 50-fold higher than in mature leaves. In addition, transcripts of MnSOD could be induced 3- to 5-fold in response to sucrose, ethephon and Murashige-Skoog salts.
Plant Mol Biol 1993 Oct
PMID:Molecular cloning, characterization and expression of Mn-superoxide dismutase from the rubber tree (Hevea brasiliensis). 821 64

Previous studies using an in vivo rabbit model in which lung tissue hypoxia/hypoperfusion was created by unilateral lung collapse for 7 days demonstrated a decrease in MnSOD activity in previously hypoxic/hypoperfused lungs. In the present study, we determined whether tissue hypoxia/hypoperfusion decreased MnSOD protein concentration or mRNA expression in the lung as well, changes that would suggest pretranslational regulation of enzyme activity. Expression of MnSOD may be critical in determining the degree of tissue injury during re-oxygenation because the mitochondrial electron transport system produces reactive oxygen species (ROS) both during hypoxia and re-oxygenation. We purified MnSOD protein from rabbit livers to a specific activity of approximately 3,500 U/mg protein and found the amino terminal sequence nearly identical to those of the rat and human MnSOD proteins. Lung MnSOD protein content was quantitated by immunoassay, and MnSOD mRNA content was determined by slot blotting. Results from five control and six experimental rabbits, the right lungs of which had been hypoxic/hypoperfused because of collapse for 7 days, demonstrated a 32% decrease (P < 0.03) in MnSOD protein content (42 +/- 8 micrograms/mg DNA in hypoxic lungs compared with 61 +/- 3 micrograms/mg DNA in contralateral lungs) that was not due to decreased numbers of mitochondria. Lung succinate dehydrogenase activity, a mitochondrial marker, did not change in hypoxic/hypoperfused lungs. The mRNA for MnSOD did not change relative to B-actin mRNA in lungs that had been hypoxic and hypoperfused for 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Dec
PMID:MnSOD protein content changes in hypoxic/hypoperfused lung tissue. 825 93

Decreased endogenous superoxide dismutase (SOD) activity has been implicated in free radical-mediated reperfusion injury of the ischemic myocardium. Antioxidant enzymes have been added to the modalities of reperfusion therapy of acute myocardial infarction based on this observation. We measured the content of MnSOD specific protein, activity of Mn and Cu, ZnSODs, and MnSOD mRNA in the working isolated rat heart subjected to various durations of ischemia and reperfusion. Recovery of mechanical function was monitored and lactate and lactic dehydrogenase released in the coronary effluent before and after ischemia were measured. In this model with reversible or irreversible myocardial injury, we noted no change in the myocardial MnSOD specific protein content and, contrary to some previous observations, no change in the activity levels of Mn or Cu,ZnSODs. Our results suggest that free radical-mediated damage in the heart during ischemia and reperfusion is probably not due to impaired activity or degradation of native SODs.
J Mol Cell Cardiol 1993 Oct
PMID:Lack of change in MnSOD during ischemia/reperfusion of isolated rat heart. 826 52

We investigated the effects of pretreatment with interleukin (IL)-1 alpha on the expression of manganous (Mn) superoxide dismutase (SOD) mRNA and reperfusion-induced arrhythmias and the size of myocardial infarct in rats. Male Wistar rats received 10 mg intraperitoneal injections of human recombinant IL-1 alpha. Their hearts were thereafter isolated at 6, 12, 24, 36 h. A Northern analysis showed that Mn-SOD mRNA was mainly expressed in the heart and slightly in kidney, but not in any other organs. The expression of Mn-SOD mRNA peaked at 6 h after the injection of IL-1 alpha. The Mn-SOD protein content was most increased 12 h after injection. In the isolated heart model, the rats were pretreated with IL-1 alpha 24 h earlier and their hearts were perfused by the Langendorff method. After 20 min of ischemia which was induced by a ligation of a coronary artery, reperfusion-induced arrhythmias were observed. There were no significant differences in the incidence of ventricular arrhythmias between the IL-1 alpha pretreated and the untreated hearts. IL-1 alpha pretreatment significantly reduced the mean duration of the ventricular arrhythmias and also delayed the onset of arrhythmias. The effect of IL-1 alpha pretreatment was also investigated in a 30-min model of ischemia followed by a 3-min reperfusion in anesthetized rats. The infarct size expressed as a percentage of the area at risk was significantly reduced in the IL-1 alpha pretreated hearts compared with the untreated hearts. The left ventricular systolic pressure increased significantly in rat hearts pretreated with IL-1 alpha. Our results therefore showed that the pretreatment with IL-1 alpha induced the overexpression of Mn-SOD mRNA in the rat hearts and also suggested that pretreatment with IL-1 alpha 24 h before ischemia reduced the risk of ischemia-reperfusion injury.
J Mol Cell Cardiol 1995 Oct
PMID:Interleukin 1 alpha-induced expression of manganous superoxide dismutase reduces myocardial reperfusion injury in the rat. 857 26

Bradyrhizobium sp. (Parasponia) strain ANU289 expresses a single Mn-SOD in both the vegetative and symbiotic states. A 500 bp sod-homologous sequence was amplified from genomic DNA of strain ANU289 using PCR. A 1.3 kb SalI fragment was subsequently cloned which contained an ORF, sodA, encoding a 23 Kd protein. This putative SOD shares considerable homology with other Mn-SODs and analysis of the sodA sequence predicts that it is expressed. A lacZ-sodA fusion complemented the SOD-deficiency of E. coli QC779 and resulted in the expression of SOD activity in both mutant and wild type E. coli. We conclude that sodA encodes the Mn-SOD of strain ANU289.
Biochem Mol Biol Int 1995 Oct
PMID:The isolation and characterisation of a gene encoding superoxide dismutase from Bradyrhizobium sp. (Parasponia) strain ANU289. 859 79


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