Superoxide dismutase 1

Superoxide dismutase

Superoxide dismutase

Structure of a human Mn superoxide dismutase 2 tetramer.[1]

Identifiers

EC number 1.15.1.1 [2]

CAS number 9054-89-1 [3]

Databases

IntEnz IntEnz view [4]

BRENDA BRENDA entry [5]

ExPASy NiceZyme view [6]

KEGG KEGG entry [7]

MetaCyc metabolic pathway [8]

PRIAM profile [9]

PDB structures RCSB PDB [10] PDBe [11] PDBsum [12]

Gene Ontology AmiGO [13] / EGO [14]

Search

PMC articles [15]

PubMed articles [16]

NCBI Protein search [17]

Superoxide dismutases (SOD, EC 1.15.1.1 [18]) are enzymes that catalyze the dismutation of superoxide intooxygen and hydrogen peroxide. Thus, they are an important antioxidant defense in nearly all cells exposed tooxygen. One of the exceedingly rare exceptions is Lactobacillus plantarum and related lactobacilli, which use adifferent mechanism.

Superoxide dismutase 2

ReactionThe 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

GeneralIrwin Fridovich and Joe McCord discovered the activity of superoxide dismutase. SOD's were previously known as agroup of metalloproteins with unknown function; for example, CuZnSOD was known as erythrocuprein and as theveterinary antiinflamatory drug "Orgotein".[19] Likewise, Brewer (1967) identified a protein that later became knownas superoxide dismutase as an indophenol oxidase by protein analysis of starch gels using the phenazine-tetrazoliumtechnique.[20]

Bovine Cu-Zn SOD subunit.[21]

Several common forms of SOD exist: they are proteins cofactoredwith copper and zinc, or manganese, iron, or nickel. Thus, thereare three major families of superoxide dismutase, depending onthe metal cofactor: Cu/Zn (which binds both copper and zinc), Feand Mn types (which bind either iron or manganese), and the Nitype, which binds nickel.

• Copper and zinc – most commonly used by eukaryotes. Thecytosols of virtually all eukaryotic cells contain an SODenzyme with copper and zinc (Cu-Zn-SOD). For example,Cu-Zn-SOD available commercially is normally purified fromthe bovine erythrocytes: The Cu-Zn enzyme is a homodimer ofmolecular weight 32,500. The bovine Cu-Zn protein was thefirst SOD structure to be solved, in 1975.[22] It is an 8-stranded"Greek key" beta-barrel, with the active site held between thebarrel and two surface loops. The two subunits are tightlyjoined back-to-back, primarily by hydrophobic and some electrostatic interactions. The ligands of the copper andzinc are six histidine and one aspartate side-chains; one histidine is shared between the two metals.[23]

• 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 inthe plastids of plants. The 3D structures of the homologous Mn and Fe superoxide dismutases have the samearrangement of alpha-helices, and their active sites contain the same type and arrangement of amino acidside-chains.

• Manganese – Chicken liver (and nearly all other) mitochondria, and many bacteria (such as E. coli), contain aform with manganese (Mn-SOD): for example, the Mn-SOD found in human mitochondria. The ligands of themanganese 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).[24]

• 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

Superoxide dismutase 3

NiSODs.[25][26]

Copper/zinc superoxide dismutase

Structure of the yeast Cu,Zn enzyme superoxide dismutase.[27]

Identifiers

Symbol Sod_Cu

Pfam PF00080 [28]

InterPro IPR001424 [29]

PROSITE PDOC00082 [30]

SCOP 1sdy [31]

SUPERFAMILY 1sdy [32]

Available protein structures:

Pfam structures [33]

PDB RCSB PDB [34]; PDBe [35]

PDBsum structure summary [36]

Iron/manganese superoxide dismutases, alpha-hairpin domain

The structure of human mitochondrial manganese superoxide dismutase, which reveals a novel tetrameric interface of two 4-helixbundles.[24]

Identifiers

Superoxide dismutase 4

Symbol Sod_Fe_N

Pfam PF00081 [37]

InterPro IPR001189 [38]

PROSITE PDOC00083 [39]

SCOP 1n0j [40]

SUPERFAMILY 1n0j [41]

Available protein structures:

Pfam structures [42]

PDB RCSB PDB [43]; PDBe [44]

PDBsum structure summary [45]

Iron/manganese superoxide dismutases, C-terminal domain

The structure of human mitochondrial manganese superoxide dismutase, which reveals a novel tetrameric interface of two 4-helixbundles.[24]

Identifiers

Symbol Sod_Fe_C

Pfam PF02777 [46]

InterPro IPR001189 [38]

PROSITE PDOC00083 [39]

SCOP 1n0j [40]

SUPERFAMILY 1n0j [41]

Available protein structures:

Pfam structures [47]

PDB RCSB PDB [48]; PDBe [49]

PDBsum structure summary [50]

Superoxide dismutase 5

Nickel-containing superoxidedismutase

Structure of nickel-containing superoxide dismutase.[26]

Identifiers

Symbol Sod_Ni

Pfam PF09055 [51]

InterPro IPR014123 [52]

Available protein structures:

Pfam structures [53]

PDB RCSB PDB [54]; PDBe [55]

PDBsum structure summary [56]

In higher plants, SOD isozymes have been localized in different cell compartments. Mn-SOD is present inmitochondria and peroxisomes. Fe-SOD has been found mainly in chloroplasts but has also been detected inperoxisomes, and CuZn-SOD has been localized in cytosol, chloroplasts, peroxisomes, and apoplast.[57][58]

HumanThree forms of superoxide dismutase are present in humans, in all other mammals, and most chordates. SOD1 islocated in the cytoplasm, SOD2 in the mitochondria, and SOD3 is extracellular. The first is a dimer (consists of twounits), 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).

Superoxide dismutase 6

SOD1, soluble

Crystallographic structure of the human SOD1 enzyme (rainbow colored N-terminus = blue, C-terminus = red) complexed with copper(blue-green sphere) and zinc (grey spheres).[59]

Identifiers

Symbol SOD1

Alt. symbols ALS, ALS1

Entrez 6647 [60]

HUGO 11179 [61]

OMIM 147450 [62]

RefSeq NM_000454 [63]

UniProt P00441 [64]

Other data

EC number 1.15.1.1 [65]

Locus Chr. 21 q22.1 [66]

SOD2, mitochondrial

Structure of the active site of human superoxide dismutase 2.[1]

Identifiers

Symbol SOD2

Superoxide dismutase 7

Alt. symbols Mn-SOD; IPO-B; MVCD6

Entrez 6648 [67]

HUGO 11180 [68]

OMIM 147460 [69]

RefSeq NM_000636 [70]

UniProt P04179 [71]

Other data

EC number 1.15.1.1 [65]

Locus Chr. 6 q25 [72]

SOD3, extracellular

Crystallographic structure of the tetrameric human SOD3 enzyme (cartoon diagram) complexed with copper and zinc cations (orangeand grey spheres respectively).[73]

Identifiers

Symbol SOD3

Alt. symbols EC-SOD; MGC20077

Entrez 6649 [74]

HUGO 11181 [75]

OMIM 185490 [76]

RefSeq NM_003102 [77]

UniProt P08294 [78]

Other data

EC number 1.15.1.1 [65]

Locus Chr. 4 pter-q21 [79]

Superoxide dismutase 8

PlantsIn higher plants, superoxide dismutase enzymes (SODs) act as antioxidants and protect cellular components frombeing oxidized by reactive oxygen species (ROS).[80] ROS can form as a result of drought, injury, herbicides andpesticides, ozone, plant metabolic activity, nutrient deficiencies, photoinhibition, temperature above and belowground, toxic metals, and UV or gamma rays.[81][82] Specifically, molecular O2 is reduced to O2

− (an ROS calledsuperoxide) when it absorbs an excited electron released from compounds of the electron transport chain. Superoxideis known to denature enzymes, oxidize lipids, and fragment DNA.[81] SODs catalyze the production of O2 and H2O2from superoxide (O2

−), which results in less harmful reactants.When acclimating to increased levels of oxidative stress, SOD concentrations typically increase with the degree ofstress conditions. The compartmentalization of different forms of SOD throughout the plant makes them counteractstress very effectively. There are three well-known and studied classes of SOD metallic coenzymes that exist inplants. First, Fe SODs consist of two species, one homodimer (containing 1-2 g Fe) and one tetramer (containing 2-4g Fe). They are thought to be the most ancient SOD metalloenzymes and are found within both prokaryotes andeukaryotes. 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 predominantly found in mitochondrion and peroxisomes. Third, Cu-Zn SODs have electrical propertiesvery different from the other two classes. These are concentrated in the chloroplast, cytosol, and in some cases theextracellular space. Note that Cu-Zn SODs provide less protection than Fe SODs when localized in thechloroplast.[80][81][82]

BacteriaHuman 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 frombeing killed.[83]

BiochemistrySimply stated, SOD out-competes damaging reactions of superoxide, thus protecting the cell from superoxidetoxicity. The reaction of superoxide with non-radicals is spin forbidden. In biological systems, this means its mainreactions are with itself (dismutation) or with another biological radical such as nitric oxide (NO) or with atransition-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 criticalcellular targets. For example, it reacts the NO radical, and makes toxic peroxynitrite. The dismutation rate is secondorder with respect to initial superoxide concentration. Thus, the half-life of superoxide, although very short at highconcentrations (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 x109 M−1s−1),[84] this reaction being only limited 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 concentrationsof 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 metabolicpathways shown to be inactivated by superoxide.[85]

Superoxide dismutase 9

PhysiologySuperoxide is one of the main reactive oxygen species in the cell. Consequently, SOD serves a key antioxidant role.The physiological importance of SODs is illustrated by the severe pathologies evident in mice genetically engineeredto lack these enzymes. Mice lacking SOD2 die several days after birth, amid massive oxidative stress.[86] Micelacking SOD1 develop a wide range of pathologies, including hepatocellular carcinoma,[87] an acceleration ofage-related muscle mass loss,[88] an earlier incidence of cataracts and a reduced lifespan. Mice lacking SOD3 do notshow any obvious defects and exhibit a normal lifespan, though they are more sensitive to hyperoxic injury.[89]

Knockout mice of any SOD enzyme are more sensitive to the lethal effects of superoxide generating drugs, such asparaquat and diquat.Drosophila lacking SOD1 have a dramatically shortened lifespan, whereas flies lacking SOD2 die before birth. SODknockdowns in C. elegans do not cause major physiological disruptions. Knockout or null mutations in SOD1 arehighly detrimental to aerobic growth in the yeast Sacchormyces cerevisiae and result in a dramatic reduction inpost-diauxic lifespan. SOD2 knockout or null mutations cause growth inhibition on respiratory carbon sources inaddition to decreased post-diauxic lifespan.Several prokaryotic SOD null mutants have been generated, including E. Coli. The loss of periplasmic CuZnSODcauses loss of virulence and might be an attractive target for new antibiotics.

Role in diseaseMutations in the first SOD enzyme (SOD1) can cause familial amyotrophic lateral sclerosis (ALS, a form of motorneuron disease).[90] [91][92][93] The most common mutation in the U.S. is A4V, while the most intensely studied isG93A. The other two isoforms of SOD have not been linked to any human diseases, however, in mice inactivation ofSOD2 causes perinatal lethality[86] and inactivation of SOD1 causes hepatocellular carcinoma.[87] Mutations inSOD1 can cause familial ALS (several pieces of evidence also show that wild-type SOD1, under conditions ofcellular stress, is implicated in a significant fraction of sporadic ALS cases, which represent 90% of ALSpatients.),[94] by a mechanism that is presently not understood, but not due to loss of enzymatic activity or a decreasein the conformational stability of the SOD1 protein. Overexpression of SOD1 has been linked to the neural disordersseen in Down syndrome.[95]

In recent years it has become more apparent that in mice the extracellular superoxide dismutase (SOD3, ecSOD) iscritical in the development of hypertension.[96][97] In other studies, diminished SOD3 activity was linked to lungdiseases such as Acute Respiratory Distress Syndrome (ARDS) or Chronic obstructive pulmonary disease(COPD).[98][99][100]

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

Pharmacological activitySOD has powerful antinflammatory activity. For example, SOD is highly effective in treatment of colonicinflammation in experimental colitis. Treatment with SOD decreases reactive oxygen species generation andoxidative stress and, thus, inhibits endothelial activation and indicate that modulation of factors that govern adhesionmolecule expression and leukocyte-endothelial interactions. Therefore, such antioxidants may be important newtherapies for the treatment of inflammatory bowel disease.[101]

Similarly, SOD has multiple pharmacological activities. E.g., it ameliorates cis-platinum-induced nephrotoxicity inrodents.[102] As "Orgotein" or "ontosein", a pharmacologically-active purified bovine liver SOD, it is also effectivein the treatment of urinary tract inflammatory disease in man.[103] For a time, bovine liver SOD even had regulatoryapproval in several European countries for such use. This was truncated, apparently by concerns about prion disease.

Superoxide dismutase 10

An SOD-mimetic agent, TEMPOL, is currently in clinical trials for radioprotection and to prevent radiation-inducedhair-loss.[104][105] TEMPOL and similar SOD-mimetic nitroxides exhibit a multiplicity of actions in diseasesinvolving oxidative stress. For a review, see Wilcox.[106]

Cosmetic usesSOD 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 studyincluding a lack of randomization, double-blinding, or placebo.[107] Superoxide dismutase is known to reversefibrosis, perhaps through reversion of myofibroblasts back to fibroblasts.[108]

References[1] PDB 1VAR (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=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 dismutasepolymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface". Biochemistry 35 (14): 4287–97.doi:10.1021/bi951892w. PMID 8605177.

[2] http:/ / www. chem. qmul. ac. uk/ iubmb/ enzyme/ EC1/ 15/ 1/ 1. html[3] http:/ / toolserver. org/ ~magnus/ cas. php?language=en& cas=9054-89-1& title=[4] http:/ / www. ebi. ac. uk/ intenz/ query?cmd=SearchEC& ec=1. 15. 1. 1[5] http:/ / www. brenda-enzymes. org/ php/ result_flat. php4?ecno=1. 15. 1. 1[6] http:/ / www. expasy. org/ enzyme/ 1. 15. 1. 1[7] http:/ / www. genome. ad. jp/ dbget-bin/ www_bget?enzyme+ 1. 15. 1. 1[8] http:/ / biocyc. org/ META/ substring-search?type=NIL& object=1. 15. 1. 1[9] http:/ / priam. prabi. fr/ cgi-bin/ PRIAM_profiles_CurrentRelease. pl?EC=1. 15. 1. 1[10] http:/ / www. rcsb. org/ pdb/ search/ smartSubquery. do?smartSearchSubtype=EnzymeClassificationQuery& Enzyme_Classification=1. 15.

1. 1[11] http:/ / www. ebi. ac. uk/ pdbe-srv/ PDBeXplore/ enzyme/ ?ec=1. 15. 1. 1[12] http:/ / www. ebi. ac. uk/ thornton-srv/ databases/ cgi-bin/ enzymes/ GetPage. pl?ec_number=1. 15. 1. 1[13] http:/ / amigo. geneontology. org/ cgi-bin/ amigo/ go. cgi?query=GO:0004784& view=details[14] http:/ / www. ebi. ac. uk/ ego/ DisplayGoTerm?id=GO:0004784& format=normal[15] http:/ / www. ncbi. nlm. nih. gov/ entrez/ query. fcgi?db=pubmed& term=1. 15. 1. 1%5BEC/

RN%20Number%5D%20AND%20pubmed%20pmc%20local%5Bsb%5D[16] http:/ / www. ncbi. nlm. nih. gov/ entrez/ query. fcgi?db=pubmed& term=1. 15. 1. 1%5BEC/ RN%20Number%5D[17] http:/ / www. ncbi. nlm. nih. gov/ protein?term=1. 15. 1. 1%5BEC/ RN%20Number%5D[18] http:/ / enzyme. expasy. org/ EC/ 1. 15. 1. 1[19] 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.[20] Brewer GJ (September 1967). "Achromatic regions of tetrazolium stained starch gels: inherited electrophoretic variation". Am. J. Hum.

Genet. 19 (5): 674–80. PMC 1706241. PMID 4292999.[21] PDB 2SOD (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=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.

[22] Richardson JS, Thomas KA, Rubin BH, Richardson DC (1975). "Crystal Structure of Bovine Cu,Zn Superoxide Dismutase at 3ÅResolution: Chain Tracing and Metal Ligands". Proc Nat Acad Sci USA 72 (4): 1349–53. doi:10.1073/pnas.72.4.1349. PMC 432531.PMID 1055410..

[23] Tainer JA, Getzoff ED, Richardson JS, Richardson DC (1983). "Structure and mechanism of copper, zinc superoxide dismutase". Nature306 (5940): 284–7. doi:10.1038/306284a0. PMID 6316150..

[24] PDB 1N0J (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=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 interfaceof two 4-helix bundles". Cell 71 (1): 107–18. doi:10.1016/0092-8674(92)90270-M. PMID 1394426.

[25] 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.

[26] PDB 1Q0M (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=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. USA 101 (23): 8569–74. doi:10.1073/pnas.0308514101. PMC 423235. PMID 15173586.

Superoxide dismutase 11

[27] PDB 1SDY (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=1SDY); Djinović K, Gatti G, Coda A et al. (December 1991)."Structure solution and molecular dynamics refinement of the yeast Cu,Zn enzyme superoxide dismutase". Acta Crystallogr. B 47 (6):918–27. doi:10.1107/S0108768191004949. PMID 1772629.

[28] http:/ / pfam. sanger. ac. uk/ family?acc=PF00080[29] http:/ / www. ebi. ac. uk/ interpro/ DisplayIproEntry?ac=IPR001424[30] http:/ / www. expasy. org/ cgi-bin/ prosite-search-ac?PDOC00082[31] http:/ / scop. mrc-lmb. cam. ac. uk/ scop/ search. cgi?tlev=fa;& amp;pdb=1sdy[32] http:/ / supfam. org/ SUPERFAMILY/ cgi-bin/ search. cgi?search_field=1sdy[33] http:/ / pfam. sanger. ac. uk/ family/ PF00080?tab=pdbBlock[34] http:/ / www. rcsb. org/ pdb/ search/ smartSubquery. do?smartSearchSubtype=PfamIdQuery& pfamID=PF00080[35] http:/ / www. ebi. ac. uk/ pdbe-srv/ PDBeXplore/ pfam/ ?pfam=PF00080[36] http:/ / www. ebi. ac. uk/ thornton-srv/ databases/ cgi-bin/ pdbsum/ GetPfamStr. pl?pfam_id=PF00080[37] http:/ / pfam. sanger. ac. uk/ family?acc=PF00081[38] http:/ / www. ebi. ac. uk/ interpro/ DisplayIproEntry?ac=IPR001189[39] http:/ / www. expasy. org/ cgi-bin/ prosite-search-ac?PDOC00083[40] http:/ / scop. mrc-lmb. cam. ac. uk/ scop/ search. cgi?tlev=fa;& amp;pdb=1n0j[41] http:/ / supfam. org/ SUPERFAMILY/ cgi-bin/ search. cgi?search_field=1n0j[42] http:/ / pfam. sanger. ac. uk/ family/ PF00081?tab=pdbBlock[43] http:/ / www. rcsb. org/ pdb/ search/ smartSubquery. do?smartSearchSubtype=PfamIdQuery& pfamID=PF00081[44] http:/ / www. ebi. ac. uk/ pdbe-srv/ PDBeXplore/ pfam/ ?pfam=PF00081[45] http:/ / www. ebi. ac. uk/ thornton-srv/ databases/ cgi-bin/ pdbsum/ GetPfamStr. pl?pfam_id=PF00081[46] http:/ / pfam. sanger. ac. uk/ family?acc=PF02777[47] http:/ / pfam. sanger. ac. uk/ family/ PF02777?tab=pdbBlock[48] http:/ / www. rcsb. org/ pdb/ search/ smartSubquery. do?smartSearchSubtype=PfamIdQuery& pfamID=PF02777[49] http:/ / www. ebi. ac. uk/ pdbe-srv/ PDBeXplore/ pfam/ ?pfam=PF02777[50] http:/ / www. ebi. ac. uk/ thornton-srv/ databases/ cgi-bin/ pdbsum/ GetPfamStr. pl?pfam_id=PF02777[51] http:/ / pfam. sanger. ac. uk/ family?acc=PF09055[52] http:/ / www. ebi. ac. uk/ interpro/ DisplayIproEntry?ac=IPR014123[53] http:/ / pfam. sanger. ac. uk/ family/ PF09055?tab=pdbBlock[54] http:/ / www. rcsb. org/ pdb/ search/ smartSubquery. do?smartSearchSubtype=PfamIdQuery& pfamID=PF09055[55] http:/ / www. ebi. ac. uk/ pdbe-srv/ PDBeXplore/ pfam/ ?pfam=PF09055[56] http:/ / www. ebi. ac. uk/ thornton-srv/ databases/ cgi-bin/ pdbsum/ GetPfamStr. pl?pfam_id=PF09055[57] Corpas FJ, Barroso JB, del Río LA (April 2001). "Peroxisomes as a source of reactive oxygen species and nitric oxide signal molecules in

plant cells" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S1360-1385(01)01898-2). Trends Plant Sci. 6 (4): 145–50.doi:10.1016/S1360-1385(01)01898-2. PMID 11286918. .

[58] Corpas FJ, Fernández-Ocaña A, Carreras A, Valderrama R, Luque F, Esteban FJ, Rodríguez-Serrano M, Chaki M, Pedrajas JR, SandalioLM, del Río LA, Barroso JB (July 2006). "The expression of different superoxide dismutase forms is cell-type dependent in olive (Oleaeuropaea L.) leaves". Plant Cell Physiol. 47 (7): 984–94. doi:10.1093/pcp/pcj071. PMID 16766574.

[59] PDB 3CQQ (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=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 (June2008). "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.

[60] http:/ / www. ncbi. nlm. nih. gov/ entrez/ query. fcgi?db=gene& amp;cmd=retrieve& amp;dopt=default& amp;list_uids=6647& rn=1[61] http:/ / www. genenames. org/ data/ hgnc_data. php?hgnc_id=11179[62] http:/ / www. omim. org/ 147450[63] http:/ / genome. ucsc. edu/ cgi-bin/ hgTracks?Submit=Submit& position=NM_000454& rn=1[64] http:/ / www. uniprot. org/ uniprot/ P00441[65] http:/ / www. genome. jp/ dbget-bin/ www_bget?enzyme+ 1. 15. 1. 1[66] http:/ / omim. org/ search?index=geneMap& search=21q22. 1[67] http:/ / www. ncbi. nlm. nih. gov/ entrez/ query. fcgi?db=gene& amp;cmd=retrieve& amp;dopt=default& amp;list_uids=6648& rn=1[68] http:/ / www. genenames. org/ data/ hgnc_data. php?hgnc_id=11180[69] http:/ / www. omim. org/ 147460[70] http:/ / genome. ucsc. edu/ cgi-bin/ hgTracks?Submit=Submit& position=NM_000636& rn=1[71] http:/ / www. uniprot. org/ uniprot/ P04179[72] http:/ / omim. org/ search?index=geneMap& search=6q25[73] PDB 2JLP (http:/ / www. rcsb. org/ pdb/ explore/ explore. do?structureId=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 collagenbinding". J. Mol. Biol. 388 (2): 310–26. doi:10.1016/j.jmb.2009.03.026. PMID 19289127.

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Superoxide dismutase 12

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External links• Online 'Mendelian Inheritance in Man' (OMIM) 105400 (http:/ / omim. org/ entry/ 105400) (ALS)• The ALS Online Database (http:/ / alsod. iop. kcl. ac. uk/ )• A short but substantive overview of SOD and its literature. (http:/ / www. worthington-biochem. com/ SODBE/

default. html)• Damage-Based Theories of Aging (http:/ / www. senescence. info/ causes_of_aging. html) Includes a discussion

of the roles of SOD1 and SOD2 in aging.• Physicians' Comm. For Responsible Med. (http:/ / www. pcrm. org)• SOD and Oxidative Stress Pathway Image (http:/ / www. sigmaaldrich. com/ life-science/ metabolomics/

enzyme-explorer/ cell-signaling-enzymes/ superoxide-dismutase. html)• Historical information on SOD research (http:/ / www. sfrbm. org/ pdf/ FRBM20year. pdf)"The evolution of Free

Radical Biology & Medicine: A 20-year history" and "Free Radical Biology & Medicine The last 20 years: Themost highly cited papers"

• JM McCord discusses the discovery of SOD (http:/ / www. garfield. library. upenn. edu/ classics1981/A1981LK85800002. pdf)

Article Sources and Contributors 14

Article Sources and ContributorsSuperoxide dismutase  Source: http://en.wikipedia.org/w/index.php?oldid=527424838  Contributors: AHands, Abergabe, Abstraktn, Aettius, Amatulic, Andre Engels, Andrejj, AndrewGNF,AngelOfSadness, Anomalocaris, Apers0n, Arcadian, Bachrach44, Balok, Banus, Barefootmatt, Baron von Zandt, Big universe, Bigbuck, Billinghurst, Boghog, Boris Barowski, BorisTM,Camrontucker, Capricorn42, Cavemanlawyer15, Ciar, Conversion script, CopperKettle, Dcrjsr, Drphilharmonic, Dwmyers, Effeietsanders, Electric goat, Elroch, Euchiasmus, Everything IsNumbers, Federix, Flavius.Aettius, Fvasconcellos, Gak, Gio69, Gtziavelis, HLob77, Hadal, Hawkgps, Headbomb, Henning Makholm, Hodja Nasreddin, JAVIER-Javier, Jag123, Jeffersonperry,Jfdwolff, Jlittle78, JohnOFL, JonHarder, Jonnyboy5, Kaboytes, Larsobrien, Lolo-xtc, Lucadino, Luk, Marj Tiefert, Maroux, Matdrodes, MattPlantPhys, Metalloid, MiPe, Michael Hardy, MiraclePen, Mpulier, Myrmeleon formicarius, NHDaysandNights, Nachoman-au, Nina Gerlach, Nishkid64, Nkatoozi, Nono64, NotWith, PaulWicks, Phil Boswell, Pproctor, Quarterduck, R'n'B, RE73,Rastarob, Rhombus, Rifleman 82, Rjwilmsi, Sbharris, Schiann, SentientSystem, Slashme, Smokefoot, Spearhead, St0w, TenOfAllTrades, Tetracube, Teutonic Tamer, TimVickers, ToNToNi,Tstokes, Virtualt333, WLU, Webridge, Xris0, 110 anonymous edits

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