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325  structures 5135  species 2  interactions 8157  sequences 14  architectures

Family: Sod_Fe_N (PF00081)

Summary: Iron/manganese superoxide dismutases, alpha-hairpin domain

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Superoxide dismutase Edit Wikipedia article

Superoxide dismutase
Superoxide dismutase 2 PDB 1VAR.png
Structure of a human Mn superoxide dismutase 2 tetramer.[1]
Identifiers
EC number 1.15.1.1
CAS number 9054-89-1
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Superoxide dismutases (SOD, EC 1.15.1.1) are enzymes that catalyze the dismutation of superoxide (O2) into oxygen and hydrogen peroxide. Thus, they are an important antioxidant defense in nearly all cells exposed to oxygen. One anomaly is Lactobacillus plantarum and related lactobacilli, which use a different mechanism.

Reaction[edit]

The SOD-catalysed dismutation of superoxide may be written with the following half-reactions :

  • M(n+1)+-SOD + O2 → Mn+-SOD + O2
  • Mn+-SOD + O2 + 2H+ → M(n+1)+-SOD + H2O2.

where M = Cu (n=1) ; Mn (n=2) ; Fe (n=2) ; Ni (n=2).

In this reaction the oxidation state of the metal cation oscillates between n and n+1.

Types[edit]

General[edit]

Irwin Fridovich and Joe McCord discovered the activity of superoxide dismutase. SODs were previously known as a group of metalloproteins with unknown function; for example, CuZnSOD was known as erythrocuprein and as the veterinary anti-inflammatory drug "Orgotein".[2] Likewise, Brewer (1967) identified a protein that later became known as superoxide dismutase as an indophenol oxidase by protein analysis of starch gels using the phenazine-tetrazolium technique.[3]

Bovine Cu-Zn SOD subunit.[4]

Several common forms of SOD exist: they are proteins cofactored with copper and zinc, or manganese, iron, or nickel. Thus, there are three major families of superoxide dismutase, depending on the metal cofactor: Cu/Zn (which binds both copper and zinc), Fe and Mn types (which bind either iron or manganese), and the Ni type, which binds nickel.

  • Copper and zinc – most commonly used by eukaryotes. The cytosols of virtually all eukaryotic cells contain an SOD enzyme with copper and zinc (Cu-Zn-SOD). For example, Cu-Zn-SOD available commercially is normally purified from the bovine erythrocytes: The Cu-Zn enzyme is a homodimer of molecular weight 32,500. The bovine Cu-Zn protein was the first SOD structure to be solved, in 1975.[5] It is an 8-stranded "Greek key" beta-barrel, with the active site held between the barrel and two surface loops. The two subunits are tightly joined back-to-back, mostly by hydrophobic and some electrostatic interactions. The ligands of the copper and zinc are six histidine and one aspartate side-chains; one histidine is bound between the two metals.[6]
  • Iron or manganese – used by prokaryotes and protists, and in mitochondria
    • Iron – E. coli and many other bacteria also contain a form of the enzyme with iron (Fe-SOD); some bacteria contain Fe-SOD, others Mn-SOD, and some contain both. (For the E. coli Fe-SOD). Fe-SOD can be found in the plastids of plants. The 3D structures of the homologous Mn and Fe superoxide dismutases have the same arrangement of alpha-helices, and their active sites contain the same type and arrangement of amino acid side-chains.
    • Manganese – Chicken liver (and nearly all other) mitochondria, and many bacteria (such as E. coli), contain a form with manganese (Mn-SOD): For example, the Mn-SOD found in human mitochondria. The ligands of the manganese ions are 3 histidine side-chains, an aspartate side-chain and a water molecule or hydroxy ligand, depending on the Mn oxidation state (respectively II and III).[7]
  • Nickel – prokaryotic. This has a hexameric structure built from right-handed 4-helix bundles, each containing N-terminal hooks that chelate a Ni ion. The Ni-hook contains the motif His-Cys-X-X-Pro-Cys-Gly-X-Tyr; it provides most of the interactions critical for metal binding and catalysis and is, therefore, a likely diagnostic of NiSODs.[8][9]
Copper/zinc superoxide dismutase
PDB 1sdy EBI.jpg
Structure of the yeast Cu,Zn enzyme superoxide dismutase.[10]
Identifiers
Symbol Sod_Cu
Pfam PF00080
InterPro IPR001424
PROSITE PDOC00082
SCOP 1sdy
SUPERFAMILY 1sdy
Iron/manganese superoxide dismutases, alpha-hairpin domain
PDB 1n0j EBI.jpg
The structure of human mitochondrial manganese superoxide dismutase, which reveals a novel tetrameric interface of two 4-helix bundles.[7]
Identifiers
Symbol Sod_Fe_N
Pfam PF00081
InterPro IPR001189
PROSITE PDOC00083
SCOP 1n0j
SUPERFAMILY 1n0j
Iron/manganese superoxide dismutases, C-terminal domain
PDB 1n0j EBI.jpg
The structure of human mitochondrial manganese superoxide dismutase, which reveals a novel tetrameric interface of two 4-helix bundles.[7]
Identifiers
Symbol Sod_Fe_C
Pfam PF02777
InterPro IPR001189
PROSITE PDOC00083
SCOP 1n0j
SUPERFAMILY 1n0j
Nickel-containing superoxide dismutase
PDB 1q0d EBI.jpg
Structure of nickel-containing superoxide dismutase.[9]
Identifiers
Symbol Sod_Ni
Pfam PF09055
InterPro IPR014123

In higher plants, SOD isozymes have been localized in different cell compartments. Mn-SOD is present in mitochondria and peroxisomes. Fe-SOD has been found mainly in chloroplasts but has also been detected in peroxisomes, and CuZn-SOD has been localized in cytosol, chloroplasts, peroxisomes, and apoplast.[11][12]

Human[edit]

Three forms of superoxide dismutase are present in humans, in all other mammals, and most chordates. SOD1 is located in the cytoplasm, SOD2 in the mitochondria, and SOD3 is extracellular. The first is a dimer (consists of two units), whereas the others are tetramers (four subunits). SOD1 and SOD3 contain copper and zinc, whereas SOD2, the mitochondrial enzyme, has manganese in its reactive centre. The genes are located on chromosomes 21, 6, and 4, respectively (21q22.1, 6q25.3 and 4p15.3-p15.1).

SOD1, soluble
HSOD1 2VR6.png
Crystallographic structure of the human SOD1 enzyme (rainbow-color N-terminus = blue, C-terminus = red) complexed with copper (blue-green sphere) and zinc (grey spheres).[13]
Identifiers
Symbol SOD1
Alt. symbols ALS, ALS1
Entrez 6647
HUGO 11179
OMIM 147450
RefSeq NM_000454
UniProt P00441
Other data
Locus Chr. 21 q22.1
SOD2, mitochondrial
SODsite.gif
Structure of the active site of human superoxide dismutase 2.[1]
Identifiers
Symbol SOD2
Alt. symbols Mn-SOD; IPO-B; MVCD6
Entrez 6648
HUGO 11180
OMIM 147460
RefSeq NM_000636
UniProt P04179
Other data
Locus Chr. 6 q25
SOD3, extracellular
SOD3 2JLP.png
Crystallographic structure of the tetrameric human SOD3 enzyme (cartoon diagram) complexed with copper and zinc cations (orange and grey spheres respectively).[14]
Identifiers
Symbol SOD3
Alt. symbols EC-SOD; MGC20077
Entrez 6649
HUGO 11181
OMIM 185490
RefSeq NM_003102
UniProt P08294
Other data
Locus Chr. 4 pter-q21

Plants[edit]

In higher plants, superoxide dismutase enzymes (SODs) act as antioxidants and protect cellular components from being oxidized by reactive oxygen species (ROS).[15] ROS can form as a result of drought, injury, herbicides and pesticides, ozone, plant metabolic activity, nutrient deficiencies, photoinhibition, temperature above and below ground, toxic metals, and UV or gamma rays.[16][17] To be specific, molecular O2 is reduced to O2 (an ROS called superoxide) when it absorbs an excited electron released from compounds of the electron transport chain. Superoxide is known to denature enzymes, oxidize lipids, and fragment DNA.[16] SODs catalyze the production of O2 and H2O2 from superoxide (O2), which results in less harmful reactants.

When acclimating to increased levels of oxidative stress, SOD concentrations typically increase with the degree of stress conditions. The compartmentalization of different forms of SOD throughout the plant makes them counteract stress very effectively. There are three well-known and -studied classes of SOD metallic coenzymes that exist in plants. First, Fe SODs consist of two species, one homodimer (containing 1-2 g Fe) and one tetramer (containing 2-4 g Fe). They are thought to be the most ancient SOD metalloenzymes and are found within both prokaryotes and eukaryotes. Fe SODs are most abundantly localized inside plant chloroplasts, where they are indigenous. Second, Mn SODs consist of a homodimer and homotetramer species each containing a single Mn(III) atom per subunit. They are found predominantly in mitochondrion and peroxisomes. Third, Cu-Zn SODs have electrical properties very different from those of the other two classes. These are concentrated in the chloroplast, cytosol, and in some cases the extracellular space. Note that Cu-Zn SODs provide less protection than Fe SODs when localized in the chloroplast.[15][16][17]

Bacteria[edit]

Human white blood cells generate superoxide and other reactive oxygen species to kill bacteria. During infection, some bacteria (e.g., Burkholderia pseudomallei) therefore produce superoxide dismutase to protect themselves from being killed.[18]

Biochemistry[edit]

Simply stated, SOD out-competes damaging reactions of superoxide, thus protecting the cell from superoxide toxicity. The reaction of superoxide with non-radicals is spin-forbidden. In biological systems, this means that its main reactions are with itself (dismutation) or with another biological radical such as nitric oxide (NO) or with a transition-series metal. The superoxide anion radical (O2) spontaneously dismutes to O2 and hydrogen peroxide (H2O2) quite rapidly (~105 M−1s−1 at pH 7). SOD is necessary because superoxide reacts with sensitive and critical cellular targets. For example, it reacts with the NO radical, and makes toxic peroxynitrite. The dismutation rate is second-order with respect to initial superoxide concentration. Thus, the half-life of superoxide, although very short at high concentrations (e.g., 0.05 seconds at 0.1mM) is actually quite long at low concentrations (e.g., 14 hours at 0.1 nM). In contrast, the reaction of superoxide with SOD is first order with respect to superoxide concentration. Moreover, superoxide dismutase has the largest kcat/KM (an approximation of catalytic efficiency) of any known enzyme (~7 x 109 M−1s−1),[19] this reaction being limited only by the frequency of collision between itself and superoxide. That is, the reaction rate is "diffusion-limited". Even at the subnanomolar concentrations achieved by the high concentrations of SOD within cells, superoxide inactivates the citric acid cycle enzyme aconitase, can poison energy metabolism, and releases potentially toxic iron. Aconitase is one of several iron-sulfur-containing (de)hydratases in metabolic pathways shown to be inactivated by superoxide.[20]

Physiology[edit]

Superoxide is one of the main reactive oxygen species in the cell. As a consequence, SOD serves a key antioxidant role. The physiological importance of SODs is illustrated by the severe pathologies evident in mice genetically engineered to lack these enzymes. Mice lacking SOD2 die several days after birth, amid massive oxidative stress.[21] Mice lacking SOD1 develop a wide range of pathologies, including hepatocellular carcinoma,[22] an acceleration of age-related muscle mass loss,[23] an earlier incidence of cataracts and a reduced lifespan. Mice lacking SOD3 do not show any obvious defects and exhibit a normal lifespan, though they are more sensitive to hyperoxic injury.[24] Knockout mice of any SOD enzyme are more sensitive to the lethal effects of superoxide-generating drugs, such as paraquat and diquat.

Drosophila lacking SOD1 have a dramatically shortened lifespan, whereas flies lacking SOD2 die before birth. SOD knockdowns in C. elegans do not cause major physiological disruptions. Knockout or null mutations in SOD1 are highly detrimental to aerobic growth in the yeast Sacchormyces cerevisiae and result in a dramatic reduction in post-diauxic lifespan. SOD2 knockout or null mutations cause growth inhibition on respiratory carbon sources in addition to decreased post-diauxic lifespan.

Several prokaryotic SOD null mutants have been generated, including E. Coli. The loss of periplasmic CuZnSOD causes loss of virulence and might be an attractive target for new antibiotics.

Role in disease[edit]

Mutations in the first SOD enzyme (SOD1) can cause familial amyotrophic lateral sclerosis (ALS, a form of motor neuron disease).[25][26][27][28] The most common mutation in the U.S. is A4V, while the most intensely studied is G93A. The other two isoforms of SOD have not been linked to any human diseases, however, in mice inactivation of SOD2 causes perinatal lethality[21] and inactivation of SOD1 causes hepatocellular carcinoma.[22] Mutations in SOD1 can cause familial ALS (several pieces of evidence also show that wild-type SOD1, under conditions of cellular stress, is implicated in a significant fraction of sporadic ALS cases, which represent 90% of ALS patients.),[29] by a mechanism that is presently not understood, but not due to loss of enzymatic activity or a decrease in the conformational stability of the SOD1 protein. Overexpression of SOD1 has been linked to the neural disorders seen in Down syndrome.[30]

In recent years, it has become more apparent that in mice the extracellular superoxide dismutase (SOD3, ecSOD) is critical in the development of hypertension.[31][32] In other studies, diminished SOD3 activity was linked to lung diseases such as Acute Respiratory Distress Syndrome (ARDS) or Chronic obstructive pulmonary disease (COPD).[33][34][35]

Superoxide dismutase is also not expressed in neural crest cells in the developing fetus. Hence, high levels of free radicals can cause damage to them and induce dysraphic anomalies (neural tube defects).

Pharmacological activity[edit]

SOD has powerful antinflammatory activity. For example, SOD is a highly effective experimental treatment of colonic inflammation in colitis[citation needed]. Treatment with SOD decreases reactive oxygen species generation and oxidative stress and, thus, inhibits endothelial activation and indicate that modulation of factors that govern adhesion molecule expression and leukocyte-endothelial interactions. Therefore, such antioxidants may be important new therapies for the treatment of inflammatory bowel disease.[36]

Likewise, SOD has multiple pharmacological activities. E.g., it ameliorates cis-platinum-induced nephrotoxicity in rodents.[37] As "Orgotein" or "ontosein", a pharmacologically-active purified bovine liver SOD, it is also effective in the treatment of urinary tract inflammatory disease in man.[38] For a time, bovine liver SOD even had regulatory approval in several European countries for such use. This was truncated by concerns about prion disease.

An SOD-mimetic agent, TEMPOL, is currently in clinical trials for radioprotection and to prevent radiation-induced hair-loss.[39][40] TEMPOL and similar SOD-mimetic nitroxides exhibit a multiplicity of actions in diseases involving oxidative stress. For a review, see Wilcox.[41]

Cosmetic uses[edit]

SOD may reduce free radical damage to skin—for example, to reduce fibrosis following radiation for breast cancer. Studies of this kind must be regarded as tentative, however, as there were not adequate controls in the study including a lack of randomization, double-blinding, or placebo.[42] Superoxide dismutase is known to reverse fibrosis, perhaps through reversion of myofibroblasts back to fibroblasts.[43][further explanation needed]

Commercial sources[edit]

SOD is commercially obtained from bovine liver, though it is also found in yeast, spinach, and chicken liver.[44]

See also[edit]

References[edit]

  1. ^ a b PDB 1VAR; Borgstahl GE, Parge HE, Hickey MJ, Johnson MJ, Boissinot M, Hallewell RA, Lepock JR, Cabelli DE, Tainer JA (April 1996). "Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface". Biochemistry 35 (14): 4287–97. doi:10.1021/bi951892w. PMID 8605177. 
  2. ^ McCord JM, Fridovich I (1988). "Superoxide dismutase: the first twenty years (1968-1988)". Free Radic. Biol. Med. 5 (5–6): 363–9. doi:10.1016/0891-5849(88)90109-8. PMID 2855736. 
  3. ^ Brewer GJ (September 1967). "Achromatic regions of tetrazolium stained starch gels: inherited electrophoretic variation". American Journal of Human Genetics 19 (5): 674–80. PMC 1706241. PMID 4292999. 
  4. ^ PDB 2SOD;Tainer JA, Getzoff ED, Beem KM, Richardson JS, Richardson DC (September 1982). "Determination and analysis of the 2 A-structure of copper, zinc superoxide dismutase". J. Mol. Biol. 160 (2): 181–217. doi:10.1016/0022-2836(82)90174-7. PMID 7175933. 
  5. ^ Richardson JS, Thomas KA, Rubin BH, Richardson DC (1975). "Crystal Structure of Bovine Cu,Zn Superoxide Dismutase at 3Å Resolution: Chain Tracing and Metal Ligands". Proc. Natl. Acad. Sci. U.S.A. 72 (4): 1349–53. doi:10.1073/pnas.72.4.1349. PMC 432531. PMID 1055410. .
  6. ^ Tainer JA, Getzoff ED, Richardson JS, Richardson DC (1983). "Structure and mechanism of copper, zinc superoxide dismutase". Nature 306 (5940): 284–7. doi:10.1038/306284a0. PMID 6316150. .
  7. ^ a b c PDB 1N0J; Borgstahl GE, Parge HE, Hickey MJ, Beyer WF Jr, Hallewell RA, Tainer JA (1992). "The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles". Cell 71 (1): 107–18. doi:10.1016/0092-8674(92)90270-M. PMID 1394426. 
  8. ^ Barondeau DP, Kassmann CJ, Bruns CK, Tainer JA, Getzoff ED (2004). "Nickel superoxide dismutase structure and mechanism". Biochemistry 43 (25): 8038–47. doi:10.1021/bi0496081. PMID 15209499. 
  9. ^ a b PDB 1Q0M; Wuerges J, Lee JW, Yim YI, Yim HS, Kang SO, Djinovic Carugo K (2004). "Crystal structure of nickel-containing superoxide dismutase reveals another type of active site". Proc. Natl. Acad. Sci. U.S.A. 101 (23): 8569–74. doi:10.1073/pnas.0308514101. PMC 423235. PMID 15173586. 
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  13. ^ PDB 3CQQ; Cao X, Antonyuk SV, Seetharaman SV, Whitson LJ, Taylor AB, Holloway SP, Strange RW, Doucette PA, Valentine JS, Tiwari A, Hayward LJ, Padua S, Cohlberg JA, Hasnain SS, Hart PJ (June 2008). "Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis". J. Biol. Chem. 283 (23): 16169–77. doi:10.1074/jbc.M801522200. PMC 2414278. PMID 18378676. 
  14. ^ PDB 2JLP; Antonyuk SV, Strange RW, Marklund SL, Hasnain SS (May 2009). "The structure of human extracellular copper-zinc superoxide dismutase at 1.7 A resolution: insights into heparin and collagen binding". J. Mol. Biol. 388 (2): 310–26. doi:10.1016/j.jmb.2009.03.026. PMID 19289127. 
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  21. ^ a b Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ (December 1995). "Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase". Nat. Genet. 11 (4): 376–81. doi:10.1038/ng1295-376. PMID 7493016. 
  22. ^ a b Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, Epstein CJ, Huang TT (January 2005). "CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life". Oncogene 24 (3): 367–80. doi:10.1038/sj.onc.1208207. PMID 15531919. 
  23. ^ Muller FL, Song W, Liu Y, Chaudhuri A, Pieke-Dahl S, Strong R, Huang TT, Epstein CJ, Roberts LJ, Csete M, Faulkner JA, Van Remmen H (June 2006). "Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy". Free Radic. Biol. Med. 40 (11): 1993–2004. doi:10.1016/j.freeradbiomed.2006.01.036. PMID 16716900. 
  24. ^ Sentman ML, Granström M, Jakobson H, Reaume A, Basu S, Marklund SL (March 2006). "Phenotypes of mice lacking extracellular superoxide dismutase and copper- and zinc-containing superoxide dismutase". J. Biol. Chem. 281 (11): 6904–9. doi:10.1074/jbc.M510764200. PMID 16377630. 
  25. ^ Milani P, Gagliardi S, Cova E, Cereda C (2011). "SOD1 Transcriptional and Posttranscriptional Regulation and Its Potential Implications in ALS.". Neurol Res Int. 2011: 458427. doi:10.1155/2011/458427. PMC 3096450. PMID 21603028. 
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  30. ^ Groner Y, Elroy-Stein O, Avraham KB, Schickler M, Knobler H, Minc-Golomb D, Bar-Peled O, Yarom R, Rotshenker S (1994). "Cell damage by excess CuZnSOD and Down syndrome". Biomed. Pharmacother. 48 (5–6): 231–40. doi:10.1016/0753-3322(94)90138-4. PMID 7999984. 
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  32. ^ Lob, HE; Marvar, PJ; Guzik, TJ; Sharma, S; McCann, LA; Weyand, C; Gordon, FJ; Harrison, DG (2010). "Induction of hypertension and peripheral inflammation by reduction of extracellular superoxide dismutase in the central nervous system". Hypertension 55 (2): 277–83, 6p following 283. doi:10.1161/HYPERTENSIONAHA.109.142646. PMC 2813894. PMID 20008675. 
  33. ^ Young, RP; Hopkins, R; Black, PN; Eddy, C; Wu, L; Gamble, GD; Mills, GD; Garrett, JE et al. (2006). "Functional variants of antioxidant genes in smokers with COPD and in those with normal lung function". Thorax 61 (5): 394–9. doi:10.1136/thx.2005.048512. PMC 2111196. PMID 16467073. 
  34. ^ Ganguly, K; Depner, M; Fattman, C; Bein, K; Oury, TD; Wesselkamper, SC; Borchers, MT; Schreiber, M et al. (2009). "Superoxide dismutase 3, extracellular (SOD3) variants and lung function". Physiological genomics 37 (3): 260–7. doi:10.1152/physiolgenomics.90363.2008. PMC 2685504. PMID 19318538. 
  35. ^ Gongora, MC; Lob, HE; Landmesser, U; Guzik, TJ; Martin, WD; Ozumi, K; Wall, SM; Wilson, DS et al. (2008). "Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: A potential mechanism underlying adult respiratory distress syndrome". The American journal of pathology 173 (4): 915–26. doi:10.2353/ajpath.2008.080119. PMC 2543061. PMID 18787098. 
  36. ^ Seguí J, Gironella M, Sans M, Granell S, Gil F, Gimeno M, Coronel P, Piqué JM, Panés J (September 2004). "Superoxide dismutase ameliorates TNBS-induced colitis by reducing oxidative stress, adhesion molecule expression, and leukocyte recruitment into the inflamed intestine". J. Leukoc. Biol. 76 (3): 537–44. doi:10.1189/jlb.0304196. PMID 15197232. 
  37. ^ McGinness JE, Proctor PH, Demopoulos HB, Hokanson JA, Kirkpatrick DS (1978). "Amelioration of cis-platinum nephrotoxicity by orgotein (superoxide dismutase)". Physiol. Chem. Phys. 10 (3): 267–77. PMID 733940. 
  38. ^ Marberger H, Huber W, Bartsch G, Schulte T, Swoboda P (1974). "Orgotein: a new antiinflammatory metalloprotein drug evaluation of clinical efficacy and safety in inflammatory conditions of the urinary tract". Int Urol Nephrol 6 (2): 61–74. PMID 4615073. 
  39. ^ [1]
  40. ^ http://clincancerres.aacrjournals.org/content/10/19/6411.full
  41. ^ Wilcox CS (May 2010). "Effects of tempol and redox-cycling nitroxides in models of oxidative stress". Pharmacol. Ther. 126 (2): 119–45. doi:10.1016/j.pharmthera.2010.01.003. PMC 2854323. PMID 20153367. 
  42. ^ Campana F, Zervoudis S, Perdereau B, Gez E, Fourquet A, Badiu C, Tsakiris G, Koulaloglou S (2004). "Topical superoxide dismutase reduces post-irradiation breast cancer fibrosis". J. Cell. Mol. Med. 8 (1): 109–16. doi:10.1111/j.1582-4934.2004.tb00265.x. PMID 15090266. 
  43. ^ Vozenin-Brotons MC, Sivan V, Gault N, Renard C, Geffrotin C, Delanian S, Lefaix JL, Martin M (January 2001). "Antifibrotic action of Cu/Zn SOD is mediated by TGF-beta1 repression and phenotypic reversion of myofibroblasts". Free Radic. Biol. Med. 30 (1): 30–42. doi:10.1016/S0891-5849(00)00431-7. PMID 11134893. 
  44. ^ Editors of Pharmacist's letter, Prescriber's letter, ed. (2007). Natural medicines comprehensive database (10th ed. ed.). Therapeutic Research Faculty. p. 1405. ISBN 0978820533. 

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Iron/manganese superoxide dismutases, alpha-hairpin domain Provide feedback

superoxide dismutases (SODs) catalyse the conversion of superoxide radicals to hydrogen peroxide and molecular oxygen. Three evolutionarily distinct families of SODs are known, of which the Mn/Fe-binding family is one. In humans, there is a cytoplasmic Cu/Zn SOD, and a mitochondrial Mn/Fe SOD. N-terminal domain is a long alpha antiparallel hairpin. A small fragment of YTRE_LEPBI matches well - sequencing error?

Literature references

  1. Knapp S, Kardinahl S, Hellgren N, Tibbelin G, Schafer G, Ladenstein R; , J Mol Biol 1999;285:689-702.: Refined crystal structure of a superoxide dismutase from the hyperthermophilic archaeon Sulfolobus acidocaldarius at 2.2 A resolution. PUBMED:9878438 EPMC:9878438


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR019831

Superoxide dismutases (SODs) (EC) catalyse the conversion of superoxide radicals to molecular oxygen. Their function is to destroy the radicals that are normally produced within cells and are toxic to biological systems. Three evolutionarily distinct families of SODs are known, of which the Mn/Fe-binding family is one [PUBMED:3315461, PUBMED:3345848, PUBMED:1556751]. This family includes both single metal-binding SODs and cambialistic SOD, which can bind either Mn or Fe. Fe/MnSODs are ubiquitous enzymes that are responsible for the majority of SOD activity in prokaryotes, fungi, blue-green algae and mitochondria. Fe/MnSODs are found as homodimers or homotetramers.

The structure of Fe/MnSODs can be divided into two domains, an alpha N-terminal domain and an alpha/beta C-terminal domain, connected by a loop. The structure of the N-terminal domain consists of a two helices in an antiparallel hairpin, with a left-handed twist [PUBMED:9537987]. The structure of the C-terminal domain is of the alpha/beta type, and consists of a three-stranded antiparallel beta-sheet in the order 213, along with four helices in the arrangement alpha/beta(2)/alpha/beta/alpha(2) [PUBMED:9931259].

This entry represents the N-terminal domain of Manganese/iron superoxide dismutase.

Gene Ontology

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Domain organisation

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(25)
Full
(8157)
Representative proteomes NCBI
(5799)
Meta
(936)
RP15
(485)
RP35
(915)
RP55
(1223)
RP75
(1451)
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Format an alignment

  Seed
(25)
Full
(8157)
Representative proteomes NCBI
(5799)
Meta
(936)
RP15
(485)
RP35
(915)
RP55
(1223)
RP75
(1451)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(25)
Full
(8157)
Representative proteomes NCBI
(5799)
Meta
(936)
RP15
(485)
RP35
(915)
RP55
(1223)
RP75
(1451)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Overington and HMM_iterative_training
Previous IDs: sodfe;
Type: Domain
Author: Eddy SR, Griffiths-Jones SR
Number in seed: 25
Number in full: 8157
Average length of the domain: 79.40 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 40.82 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.1 21.1
Trusted cut-off 21.1 21.1
Noise cut-off 20.9 20.9
Model length: 82
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

Sod_Fe_C Sod_Fe_N

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Sod_Fe_N domain has been found. There are 325 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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