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Biochimica Et Biophysica Acta Feb 2010The discovery of superoxide dismutases (SODs), which convert superoxide radicals to molecular oxygen and hydrogen peroxide, has been termed the most important discovery... (Review)
Review
The discovery of superoxide dismutases (SODs), which convert superoxide radicals to molecular oxygen and hydrogen peroxide, has been termed the most important discovery of modern biology never to win a Nobel Prize. Here, we review the reasons this discovery has been underappreciated, as well as discuss the robust results supporting its premier biological importance and utility for current research. We highlight our understanding of SOD function gained through structural biology analyses, which reveal important hydrogen-bonding schemes and metal-binding motifs. These structural features create remarkable enzymes that promote catalysis at faster than diffusion-limited rates by using electrostatic guidance. These architectures additionally alter the redox potential of the active site metal center to a range suitable for the superoxide disproportionation reaction and protect against inhibition of catalysis by molecules such as phosphate. SOD structures may also control their enzymatic activity through product inhibition; manipulation of these product inhibition levels has the potential to generate therapeutic forms of SOD. Markedly, structural destabilization of the SOD architecture can lead to disease, as mutations in Cu,ZnSOD may result in familial amyotrophic lateral sclerosis, a relatively common, rapidly progressing and fatal neurodegenerative disorder. We describe our current understanding of how these Cu,ZnSOD mutations may lead to aggregation/fibril formation, as a detailed understanding of these mechanisms provides new avenues for the development of therapeutics against this so far untreatable neurodegenerative pathology.
Topics: Amino Acid Sequence; Animals; Humans; Molecular Sequence Data; Sequence Homology, Amino Acid; Superoxide Dismutase
PubMed: 19914407
DOI: 10.1016/j.bbapap.2009.11.004 -
Biological Research 2009Free radicals are extremely reactive and produce damage and modify cell functions. Furthermore, superoxide dismutase and catalase are believed to play a key role in the...
Free radicals are extremely reactive and produce damage and modify cell functions. Furthermore, superoxide dismutase and catalase are believed to play a key role in the enzymatic defence of the cells. Indeed, some authors have argued that reduced free-radical damage could explain increased longevity. Margaritifera margaritifera is one of the longest-lived animals in the world (up to 100-200 years). Furthermore, this organism may serve as a useful model for gerontologists interested in exploring the mechanisms that promote long life and the slowing of senescence. The present study estimated for the first time individual enzymatic activity for superoxide dismutase isozymes (Cu,Zn-SOD and Mn-SOD) and catalase in tissue preparations of gills, digestive glands and mantles of two natural populations of M. margaritifera. Superoxide dismutase activities showed significant differences in the tissues analysed of specimens from the same river and in specimens from different rivers for the same tissue. Catalase activity levels also showed significant variation, but differences among tissues, within tissues or between rivers were of relatively little interest. We failed to find any relationship between individual enzymatic activities and the age estimated for each mussel. Indeed, the wide variation found in activity levels can be principally interpreted as an adaptation to the unpredictable and changing nature of freshwater natural habitats.
Topics: Aging; Animals; Bivalvia; Catalase; Rivers; Superoxide Dismutase; Tissue Distribution
PubMed: 19621133
DOI: No ID Found -
Journal of Bacteriology Apr 1978Streptococcus faecalis contains a single superoxide dismutase that has been purified to homogeneity with a 55% yield. This enzyme has a molecular weight of 45,000 and is...
Streptococcus faecalis contains a single superoxide dismutase that has been purified to homogeneity with a 55% yield. This enzyme has a molecular weight of 45,000 and is composed of two subunits of equal size. It contains 1.3 atoms of manganese per molecule. Its amino acid composition was determined and is compared with that for the superoxide dismutases from Escherichia coli, Streptococcus mutans, and Mycobacterium lepraemurium. When used as an antigen in rabbits, the S. faecalis enzyme elicited the formation of a precipitating and inhibiting antibody. This antibody cross-reacted with the superoxide dismutase present in another strain of S. faecalis, but neither inhibited nor precipitated the superoxide dismutases in a wide range of other bacteria, including several other streptococci, such as S. pyogenes, S. pneumoniae, and S. lactis. The inhibiting antibody was used to suppress the superoxide dismutase activity present in cell extracts of S. faecalis and thus allow the demonstration that 17% of the total oxygen consumption by such extracts, in the presence of reduced nicotinamide adenine dinucleotide, was associated with the production of O(2) (-). A variety of bacterial species were surveyed for their content of superoxide dismutases. The iron-containing enzyme was distinguished from the manganese-containing enzyme through the use of H(2)O(2), which inactivates the former more readily than the latter. Some of the bacteria appeared to contain only the iron enzyme, others only the manganese enzyme, and still others both. Indeed, some had multiple, electrophoretically distinct superoxide dismutases in both categories. There was no discernible absolute relationship between the types of superoxide dismutases in a particular organism and their Gram-stain reaction.
Topics: Amino Acids; Bacteria; Enterococcus faecalis; Molecular Weight; Oxygen Consumption; Streptococcus; Streptomycin; Superoxide Dismutase; Superoxides
PubMed: 206536
DOI: 10.1128/jb.134.1.229-236.1978 -
FEMS Immunology and Medical Microbiology Sep 2005Manganese-containing superoxide dismutases (MnSODs) are ubiquitous metalloenzymes involved in cell defence against endogenous and exogenous reactive oxygen species. In... (Review)
Review
Manganese-containing superoxide dismutases (MnSODs) are ubiquitous metalloenzymes involved in cell defence against endogenous and exogenous reactive oxygen species. In fungi, using this essential enzyme for phylogenetic analysis of Pneumocystis and Ganoderma genera, and of species selected among Ascomycota, Basidiomycota and Zygomycota, provided interesting results in taxonomy and evolution. The role of mitochondrial and cytosolic MnSODs was explored in some pathogenic Basidiomycota yeasts (Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. gattii, Malassezia sympodialis), Ascomycota filamentous fungi (Aspergillus fumigatus), and Ascomycota yeasts (Candida albicans). MnSOD-based phylogenetic and pathogenic data are confronted in order to evaluate the roles of fungal MnSODs in pathophysiological mechanisms.
Topics: Ascomycota; Basidiomycota; Mycoses; Phylogeny; Superoxide Dismutase
PubMed: 16055318
DOI: 10.1016/j.femsim.2005.06.003 -
International Journal of Molecular... Jun 2022Superoxide dismutases (SODs), a family of antioxidant enzymes, are the first line of defense against oxidative damage and are ubiquitous in every cell of all plant...
Superoxide dismutases (SODs), a family of antioxidant enzymes, are the first line of defense against oxidative damage and are ubiquitous in every cell of all plant types. The Cu/Zn SOD, one of three types of SODs present in plant species, is involved in many of the biological functions of plants in response to abiotic and biotic stresses. Here, we carried out a comprehensive analysis of the Cu/Zn SOD gene family in different plant species, ranging from lower plants to higher plants, and further investigated their organization, sequence features, and expression patterns in response to biotic and abiotic stresses. Our results show that plant Cu/Zn SODs can be divided into two subfamilies (group I and group II). Group II appeared to be conserved only as single- or low-copy genes in all lineages, whereas group I genes underwent at least two duplication events, resulting in multiple gene copies and forming three different subgroups (group Ia, group Ib, and group Ic). We also found that, among these genes, two important events-the loss of introns and the loss of and variation in signal peptides-occurred over the long course of their evolution, indicating that they were involved in shifts in subcellular localization from the chloroplast to cytosol or peroxisome and underwent functional divergence. In addition, expression patterns of Cu/Zn SOD genes from and were tested in different tissues/organs and developmental stages and under different abiotic stresses. The results indicate that the Cu/Zn SOD gene family possesses potential functional divergence and may play vital roles in ROS scavenging in response to various stresses in plants. This study will help establish a foundation for further understanding these genes' function during stress responses.
Topics: Arabidopsis; Evolution, Molecular; Phylogeny; Stress, Physiological; Superoxide Dismutase; Superoxide Dismutase-1; Zinc
PubMed: 35806085
DOI: 10.3390/ijms23137082 -
The Biochemical Journal Sep 1984The contents of extracellular superoxide dismutase, CuZn superoxide dismutase and Mn superoxide dismutase were determined in tissues from nine mammalian species. The...
The contents of extracellular superoxide dismutase, CuZn superoxide dismutase and Mn superoxide dismutase were determined in tissues from nine mammalian species. The pattern of CuZn superoxide dismutase distribution was similar in all species, with high activity in metabolically active organs such as liver and kidney and low activity in, for example, skeletal muscle. Mn superoxide dismutase activity was high in organs with high respiration, such as liver, kidney, and myocardium. Overall the Mn superoxide dismutase activity in organs was almost as high as the CuZn superoxide dismutase activity. The content of extracellular superoxide dismutase was, almost without exception, lower than the content of the other isoenzymes. The pattern of tissue distribution was distinctly different from those of CuZn superoxide dismutase and Mn superoxide dismutase. The tissue distribution of extracellular superoxide dismutase differed among species, but in general there was much in lungs and kidneys and little in skeletal muscle. In man, pig, sheep, cow, rabbit and mouse the overall tissue extracellular superoxide dismutase activities were similar to each other, whereas dog, cat and rat tissues contained distinctly less. There was no general correlation between the tissue extracellular superoxide dismutase activity of any of the various species and the variable plasma activity. The ratio between the plasma and the overall tissue activities was high, for some species over unity, providing further evidence for the notion that one role of extracellular superoxide dismutase is as a plasma protein.
Topics: Animals; Cats; Cattle; Chromatography, Gel; Dogs; Extracellular Space; Humans; Isoenzymes; Mice; Rabbits; Rats; Sheep; Species Specificity; Superoxide Dismutase; Swine; Tissue Distribution
PubMed: 6487268
DOI: 10.1042/bj2220649 -
Biophysical Journal Apr 2020The folding reaction of a stable monomeric variant of Cu/Zn superoxide dismutase (mSOD1), an enzyme responsible for the conversion of superoxide free radicals into...
The folding reaction of a stable monomeric variant of Cu/Zn superoxide dismutase (mSOD1), an enzyme responsible for the conversion of superoxide free radicals into hydrogen peroxide and oxygen, is known to be among the slowest folding processes that adhere to two-state behavior. The long lifetime, ∼10 s, of the unfolded state presents ample opportunities for the polypeptide chain to transiently sample nonnative structures before the formation of the productive folding transition state. We recently observed the formation of a nonnative structure in a peptide model of the C-terminus of SOD1, a sequence that might serve as a potential source of internal chain friction-limited folding. To test for friction-limited folding, we performed a comprehensive thermodynamic and kinetic analysis of the folding mechanism of mSOD1 in the presence of the viscogens glycerol and glucose. Using a, to our knowledge, novel analysis of the folding reactions, we found the disulfide-reduced form of the protein that exposes the C-terminal sequence, but not its disulfide-oxidized counterpart that protects it, experiences internal chain friction during folding. The sensitivity of the internal friction to the disulfide bond status suggests that one or both of the cross-linked regions play a critical role in driving the friction-limited folding. We speculate that the molecular mechanisms giving rise to the internal friction of disulfide-reduced mSOD1 might play a role in the amyotrophic lateral sclerosis-linked aggregation of SOD1.
Topics: Amyotrophic Lateral Sclerosis; Disulfides; Friction; Humans; Kinetics; Mutation; Protein Folding; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 32191862
DOI: 10.1016/j.bpj.2020.02.028 -
Genomics Jan 2020Climatic change induced heat stress causes a formidable challenge for maintaining optimum productivity in goats. The SOD1 gene (superoxide dismutase 1) is one of the...
Climatic change induced heat stress causes a formidable challenge for maintaining optimum productivity in goats. The SOD1 gene (superoxide dismutase 1) is one of the genes that regulates the heat tolerance capacity. This study aimed to in silico characterize this gene. Sequence based phylogenetic tree analysis showed the caprine SOD1 gene has close evolutional relationship with that of sheep. STRING database reveals its interaction with SOD2 (Superoxide dismutase [Mn], mitochondrial), ATOX1 (Copper transport protein), RAC1 (Ras-related C3 botulinum toxin substrate 1), GPX2 (Glutathione peroxidase 2), GPX4 (Glutathione peroxidase 4), GPX5, GPX6, CAT (Catalase). The KEGG pathway maps gave interaction with eNOS, iNOS, VEGF and MAPK in which gene transcription modulates response to heat stress. The three dimensional protein structure was predicted using Modeller, Phyre 2, and Swiss Model. Structure validation was done observing the Ramachandran Plot and Hydrophobicity Plot in Discovery Studio considering amino acid residues in favoured region.
Topics: Animals; Computer Simulation; Goats; Hydrophobic and Hydrophilic Interactions; Ligands; Models, Molecular; Phylogeny; Protein Conformation; Protein Interaction Mapping; Superoxide Dismutase-1
PubMed: 30684533
DOI: 10.1016/j.ygeno.2019.01.016 -
Inorganic Chemistry Mar 2013The active-site structures of the oxidized and reduced forms of manganese-substituted iron superoxide dismutase (Mn(Fe)SOD) are examined, for the first time, using a...
The active-site structures of the oxidized and reduced forms of manganese-substituted iron superoxide dismutase (Mn(Fe)SOD) are examined, for the first time, using a combination of spectroscopic and computational methods. On the basis of electronic absorption, circular dichroism (CD), magnetic CD (MCD), and variable-temperature variable-field MCD data obtained for oxidized Mn(Fe)SOD, we propose that the active site of this species is virtually identical to that of wild-type manganese SOD (MnSOD), with both containing a metal ion that resides in a trigonal bipyramidal ligand environment. This proposal is corroborated by quantum mechanical/molecular mechanical (QM/MM) computations performed on complete protein models of Mn(Fe)SOD in both its oxidized and reduced states and, for comparison, wild-type (WT) MnSOD. The major differences between the QM/MM optimized active sites of WT MnSOD and Mn(Fe)SOD are a smaller (His)N-Mn-N(His) equatorial angle and a longer (Gln146(69))NH···O(sol) H-bond distance in the metal-substituted protein. Importantly, these modest geometric differences are consistent with our spectroscopic data obtained for the oxidized proteins and high-field electron paramagnetic resonance spectra reported previously for reduced Mn(Fe)SOD and MnSOD. As Mn(Fe)SOD exhibits a reduction midpoint potential (E(m)) almost 700 mV higher than that of MnSOD, which has been shown to be sufficient for explaining the lack of SOD activity displayed by the metal-subtituted species (Vance, C. K.; Miller, A. F. Biochemistry 2001, 40, 13079-13087), E(m)'s were computed for our experimentally validated QM/MM optimized models of Mn(Fe)SOD and MnSOD. These computations properly reproduce the experimental trend and reveal that the drastically elevated E(m) of the metal substituted protein stems from a larger separation between the second-sphere Gln residue and the coordinated solvent in Mn(Fe)SOD relative to MnSOD, which causes a weakening of the corresponding H-bond interaction in the oxidized state and alleviates steric crowding in the reduced state.
Topics: Catalytic Domain; Electrons; Manganese; Models, Molecular; Oxidation-Reduction; Spectrum Analysis; Superoxide Dismutase
PubMed: 23461587
DOI: 10.1021/ic302867y -
Yakugaku Zasshi : Journal of the... 2014Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are thought to involve lung injury induced by reactive oxygen species (ROS), in... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are thought to involve lung injury induced by reactive oxygen species (ROS), in particular superoxide anion. The enzyme, superoxide dismutase (SOD) catalyses the dismutation of superoxide anion to hydrogen peroxide. Lecithinized SOD (PC-SOD) has overcome a number of previous clinical limitations of SOD, including low tissue affinity and low stability in plasma. Recent animal studies suggest that PC-SOD is effective for the treatment of IPF and COPD. We are now performing the clinical study of PC-SOD for IPF patients.
Topics: Animals; Bleomycin; Humans; Phosphatidylcholines; Pulmonary Disease, Chronic Obstructive; Superoxide Dismutase
PubMed: 24389620
DOI: 10.1248/yakushi.13-00221-4