Editing Superoxide dismutase (section)

== Types ==

=== General ===
{{Further|Nickel superoxide dismutase|Iron superoxide dismutase}}
[[Irwin Fridovich]] and [[Joe M. McCord|Joe McCord]] at [[Duke University]] discovered the enzymatic activity of superoxide dismutase in 1968.<ref name="sodCat">{{cite journal | vauthors = McCord JM, Fridovich I | title = Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein) | journal = The Journal of Biological Chemistry | volume = 244 | issue = 22 | pages = 6049–6055 | date = November 1969 | pmid = 5389100 | doi = 10.1016/S0021-9258(18)63504-5 | doi-access = free }}</ref> SODs were previously known as a group of [[metalloprotein]]s with unknown function; for example, CuZnSOD was known as erythrocuprein (or hemocuprein, or cytocuprein) or as the veterinary anti-inflammatory drug "Orgotein".<ref name="pmid2855736">{{cite journal | vauthors = McCord JM, Fridovich I | title = Superoxide dismutase: the first twenty years (1968–1988) | journal = Free Radical Biology & Medicine | volume = 5 | issue = 5–6 | pages = 363–369 | year = 1988 | pmid = 2855736 | doi = 10.1016/0891-5849(88)90109-8 }}</ref> 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.<ref name="pmid4292999">{{cite journal | vauthors = Brewer GJ | title = Achromatic regions of tetrazolium stained starch gels: inherited electrophoretic variation | journal = American Journal of Human Genetics | volume = 19 | issue = 5 | pages = 674–680 | date = September 1967 | pmid = 4292999 | pmc = 1706241 }}</ref>

There are three major families of superoxide dismutase, depending on the protein fold and the metal [[Cofactor (biochemistry)|cofactor]]: the Cu/Zn type (which binds both copper and [[zinc]]), Fe and Mn types (which bind either iron or [[manganese]]), and the Ni type (which binds [[nickel]]).
{|
|- valign=top
| [[Image:2SOD ribbon colorPencil WhBkgd.png|thumb|right|[[Ribbon diagram]] of bovine Cu-Zn SOD subunit<ref name="pmid7175933">{{PDB|2SOD}};{{cite journal | vauthors = Tainer JA, Getzoff ED, Beem KM, Richardson JS, Richardson DC | title = Determination and analysis of the 2 A-structure of copper, zinc superoxide dismutase | journal = Journal of Molecular Biology | volume = 160 | issue = 2 | pages = 181–217 | date = September 1982 | pmid = 7175933 | doi = 10.1016/0022-2836(82)90174-7 | author-link2 = Elizabeth D. Getzoff }}</ref>]]
| [[File:Crystal Structure of Human Manganese SOD.png|thumb|right|Active site of Human Manganese SOD, manganese shown in purple<ref name="pmid16443160">{{cite journal | vauthors = Quint P, Reutzel R, Mikulski R, McKenna R, Silverman DN | title = Crystal structure of nitrated human manganese superoxide dismutase: mechanism of inactivation | journal = Free Radical Biology & Medicine | volume = 40 | issue = 3 | pages = 453–458 | date = February 2006 | pmid = 16443160 | doi = 10.1016/j.freeradbiomed.2005.08.045 }}</ref>]]
| [[File:094-SuperoxideDismutase-Mn Fe 2mers.png|thumb|right|Mn-SOD vs Fe-SOD dimers]]
|}

* Copper and zinc – most commonly used by [[eukaryote]]s, including humans. The [[cytosol]]s of virtually all [[eukaryote|eukaryotic]] cells contain a SOD enzyme with copper and [[zinc]] (Cu-Zn-SOD). For example, Cu-Zn-SOD available commercially is normally purified from bovine red blood cells. The bovine Cu-Zn enzyme is a homodimer of molecular weight 32,500. It was the first SOD whose atomic-detail crystal structure was solved, in 1975.<ref name="1SOD">{{cite journal | vauthors = Richardson J, Thomas KA, Rubin BH, Richardson DC | title = Crystal structure of bovine Cu,Zn superoxide dismutase at 3 A resolution: chain tracing and metal ligands | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 72 | issue = 4 | pages = 1349–1353 | date = April 1975 | pmid = 1055410 | pmc = 432531 | doi = 10.1073/pnas.72.4.1349 | doi-access = free }}.</ref> It is an 8-stranded "[[Greek key (protein structure)|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.<ref name="pmid6316150">{{cite journal | vauthors = Tainer JA, Getzoff ED, Richardson JS, Richardson DC | title = Structure and mechanism of copper, zinc superoxide dismutase | journal = Nature | volume = 306 | issue = 5940 | pages = 284–287 | year = 1983 | pmid = 6316150 | doi = 10.1038/306284a0 | s2cid = 4266810 | bibcode = 1983Natur.306..284T }}</ref> 
*[[File:Iron Superoxide Dismutase Active Site.png|thumb|241x241px|Active site for iron superoxide dismutase]]Iron or manganese – used by [[prokaryote]]s and [[protist]]s, and in [[mitochondria]] and [[chloroplast]]s
** Iron – Many bacteria contain a form of the enzyme with iron (Fe-SOD); some bacteria contain Fe-SOD, others Mn-SOD, and some (such as ''[[Escherichia coli|E. coli]]'') contain both. Fe-SOD can also be found in the [[plastid|chloroplasts]] 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. They are usually dimers, but occasionally tetramers.
** Manganese – Nearly all [[mitochondria]], and many bacteria, 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 [[Hydroxyl|hydroxy]] [[ligand]], depending on the Mn oxidation state (respectively II and III).<ref name="pmid1394426">{{PDB|1N0J}}; {{cite journal | vauthors = Borgstahl GE, Parge HE, Hickey MJ, Beyer WF, Hallewell RA, Tainer JA | title = The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles | journal = Cell | volume = 71 | issue = 1 | pages = 107–118 | date = October 1992 | pmid = 1394426 | doi = 10.1016/0092-8674(92)90270-M | s2cid = 41611695 }}</ref>
* Nickel – [[prokaryotic]]. This has a hexameric (6-copy) 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.<ref name ="pmid15209499">{{cite journal | vauthors = Barondeau DP, Kassmann CJ, Bruns CK, Tainer JA, Getzoff ED | title = Nickel superoxide dismutase structure and mechanism | journal = Biochemistry | volume = 43 | issue = 25 | pages = 8038–8047 | date = June 2004 | pmid = 15209499 | doi = 10.1021/bi0496081 | s2cid = 10700340 }}</ref><ref name ="pmid15173586">{{PDB|1Q0M}}; {{cite journal | vauthors = Wuerges J, Lee JW, Yim YI, Yim HS, Kang SO, Djinovic Carugo K | title = Crystal structure of nickel-containing superoxide dismutase reveals another type of active site | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 23 | pages = 8569–8574 | date = June 2004 | pmid = 15173586 | pmc = 423235 | doi = 10.1073/pnas.0308514101 | doi-access = free | bibcode = 2004PNAS..101.8569W }}</ref>

{|
|- valign=top
|{{Infobox protein family
| Symbol = Sod_Cu
| Name = Copper/zinc superoxide dismutase
| image = 1sdy CuZnSOD dimer ribbon.png
| width = 
| caption = Yeast Cu,Zn superoxide dismutase dimer<ref name="pmid1772629">{{PDB|1SDY}}; {{cite journal | vauthors = Djinović K, Gatti G, Coda A, Antolini L, Pelosi G, Desideri A, Falconi M, Marmocchi F, Rolilio G, Bolognesi M | display-authors = 6 | title = Structure solution and molecular dynamics refinement of the yeast Cu,Zn enzyme superoxide dismutase | journal = Acta Crystallographica Section B: Structural Science | volume = 47 ( Pt 6) | issue = 6 | pages = 918–927 | date = December 1991 | pmid = 1772629 | doi = 10.1107/S0108768191004949 | bibcode = 1991AcCrB..47..918D | doi-access = free }}</ref>
| Pfam = PF00080
| InterPro = IPR001424
| SMART = 
| PROSITE = PDOC00082
| SCOP =1sdy
| TCDB = 
| OPM family = 
| OPM protein = 
}}
|{{Infobox protein family
| Symbol = Sod_Fe_N
| Name = Iron/manganese superoxide dismutases, alpha-hairpin domain
| image = 1n0j H mit MnSOD D1 rib.png
| width = 
| caption = Structure of domain1 (color), human mitochondrial Mn superoxide dismutase<ref name="pmid1394426" />
| Pfam = PF00081
| InterPro = IPR001189
| SMART = 
| PROSITE = PDOC00083
| SCOP = 1n0j
| TCDB = 
| OPM family = 
| OPM protein = 
}}
|{{Infobox protein family
| Symbol = Sod_Fe_C
| Name = Iron/manganese superoxide dismutases, C-terminal domain
| image = 1n0j H mit MnSOD D2 rib.png
| width = 
| caption = Structure of domain2 (color), human mitochondrial Mn superoxide dismutase<ref name="pmid1394426" />
| Pfam = PF02777
| InterPro = IPR001189
| SMART = 
| PROSITE = PDOC00083
| SCOP = 1n0j
| TCDB = 
| OPM family = 
| OPM protein = 
}}
|{{Infobox protein family
| Symbol = Sod_Ni
| Name = Nickel superoxide dismutase
| image = 094-SuperoxideDismutase-Ni 6mer.png
| width = 
| caption = Structure of ''[[Streptomyces]]'' Ni superoxide dismutase hexamer<ref name="pmid15173586" />
| Pfam = PF09055
| InterPro = IPR014123
| SMART = 
| PROSITE = 
| SCOP = 1q0d
| TCDB = 
| OPM family = 
| OPM protein = 
}}
|}

In higher plants, SOD isozymes have been localized in different cell compartments. Mn-SOD is present in mitochondria and [[peroxisome]]s. 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]].<ref name="pmid11286918">{{cite journal | vauthors = Corpas FJ, Barroso JB, del Río LA | title = Peroxisomes as a source of reactive oxygen species and nitric oxide signal molecules in plant cells | journal = Trends in Plant Science | volume = 6 | issue = 4 | pages = 145–150 | date = April 2001 | pmid = 11286918 | doi = 10.1016/S1360-1385(01)01898-2 | bibcode = 2001TPS.....6..145C }}</ref><ref name="pmid16766574">{{cite journal | vauthors = Corpas FJ, Fernández-Ocaña A, Carreras A, Valderrama R, Luque F, Esteban FJ, Rodríguez-Serrano M, Chaki M, Pedrajas JR, Sandalio LM, del Río LA, Barroso JB | display-authors = 6 | title = The expression of different superoxide dismutase forms is cell-type dependent in olive (Olea europaea L.) leaves | journal = Plant & Cell Physiology | volume = 47 | issue = 7 | pages = 984–994 | date = July 2006 | pmid = 16766574 | doi = 10.1093/pcp/pcj071 | doi-access = free }}</ref>

=== Human ===

There are three forms of superoxide dismutase present in humans, in all other [[mammals]], and most [[chordates]]. [[SOD1]] is located in the [[cytoplasm]], [[SOD2]] in the [[mitochondrion|mitochondria]], and [[SOD3]] is [[extracellular]]. The first is a [[protein dimer|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 [[gene]]s are located on chromosomes 21, 6, and 4, respectively (21q22.1, 6q25.3 and 4p15.3-p15.1).
{|
|- valign=top
|{{infobox protein
| Name = [[SOD1|SOD1, soluble]]
| caption = Crystal structure of the human SOD1 enzyme (rainbow-color [[N-terminus]] = blue, [[C-terminus]] = red) complexed with copper (orange sphere) and zinc (grey sphere)<ref name="pmid">{{PDB|3CQQ}}; {{cite journal | vauthors = 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 | display-authors = 6 | title = Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis | journal = The Journal of Biological Chemistry | volume = 283 | issue = 23 | pages = 16169–16177 | date = June 2008 | pmid = 18378676 | pmc = 2414278 | doi = 10.1074/jbc.M801522200 | doi-access = free }}</ref>
| image = 2c9v CuZn rib n site.png
| width =
| HGNCid = 11179
| Symbol = [[SOD1]]
| AltSymbols = ALS, ALS1
| EntrezGene = 6647
| OMIM = 147450
| RefSeq = NM_000454
| UniProt = P00441
| PDB =
| ECnumber = 1.15.1.1
| Chromosome = 21
| Arm = q
| Band = 22.1
| LocusSupplementaryData =
}}
|{{infobox protein
| Name = [[SOD2|SOD2, mitochondrial]]
| caption = Active site of human mitochondrial Mn superoxide dismutase (SOD2)<ref name="pmid8605177">{{PDB|1VAR}}; {{cite journal | vauthors = Borgstahl GE, Parge HE, Hickey MJ, Johnson MJ, Boissinot M, Hallewell RA, Lepock JR, Cabelli DE, Tainer JA | display-authors = 6 | title = Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface | journal = Biochemistry | volume = 35 | issue = 14 | pages = 4287–4297 | date = April 1996 | pmid = 8605177 | doi = 10.1021/bi951892w | s2cid = 7450190 }}</ref>
| image = SODsite.gif
| width =
| HGNCid = 11180
| Symbol = [[SOD2]]
| AltSymbols = Mn-SOD; IPO-B; MVCD6
| EntrezGene = 6648
| OMIM = 147460
| RefSeq = NM_000636
| UniProt = P04179
| PDB =
| ECnumber = 1.15.1.1
| Chromosome = 6
| Arm = q
| Band = 25
| LocusSupplementaryData =
}}
|{{infobox protein
| Name = [[SOD3|SOD3, extracellular]]
| caption = Crystallographic structure of the tetrameric human SOD3 enzyme (cartoon diagram) complexed with copper and zinc cations (orange and grey spheres respectively)<ref name="pmid19289127">{{PDB|2JLP}}; {{cite journal | vauthors = Antonyuk SV, Strange RW, Marklund SL, Hasnain SS | title = The structure of human extracellular copper-zinc superoxide dismutase at 1.7 A resolution: insights into heparin and collagen binding | journal = Journal of Molecular Biology | volume = 388 | issue = 2 | pages = 310–326 | date = May 2009 | pmid = 19289127 | doi = 10.1016/j.jmb.2009.03.026 }}</ref>
| image = SOD3_2JLP.png
| width =
| HGNCid = 11181
| Symbol = [[SOD3]]
| AltSymbols = EC-SOD; MGC20077
| EntrezGene = 6649
| OMIM = 185490
| RefSeq = NM_003102
| UniProt = P08294
| PDB =
| ECnumber = 1.15.1.1
| Chromosome = 4
| Arm = p
| Band = ter
| LocusSupplementaryData = -q21
}}
|}

=== Plants ===

In [[higher plants]], superoxide dismutase enzymes (SODs) act as antioxidants and protect cellular components from being oxidized by [[reactive oxygen species]] (ROS).<ref name="Alscher">{{cite journal | vauthors = Alscher RG, Erturk N, Heath LS | title = Role of superoxide dismutases (SODs) in controlling oxidative stress in plants | journal = Journal of Experimental Botany | volume = 53 | issue = 372 | pages = 1331–1341 | date = May 2002 | pmid = 11997379 | doi = 10.1093/jexbot/53.372.1331 | doi-access = free }}</ref> 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.<ref name="Smirnoff">{{cite journal | vauthors = Smirnoff N | title = The role of active oxygen in the response of plants to water deficit and desiccation | journal = The New Phytologist | volume = 125 | issue = 1 | pages = 27–58 | date = September 1993 | pmid = 33874604 | doi = 10.1111/j.1469-8137.1993.tb03863.x | doi-access = free | bibcode = 1993NewPh.125...27S }}</ref><ref name="Raychaudhuri">{{cite journal | vauthors = Raychaudhuri SS, Deng XW | title = The Role of Superoxide Dismutase in Combating Oxidative Stress in Higher Plants | journal = The Botanical Review | volume = 66 | issue = 1| pages = 89–98 | year = 2008 | doi = 10.1007/BF02857783 | s2cid = 7663001 }}</ref> To be specific, molecular O<sub>2</sub> is reduced to {{chem|O|2|-}} (a 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.<ref name="Smirnoff"/> SODs catalyze the production of O<sub>2</sub> and {{chem|H|2|O|2}} from superoxide ({{chem|O|2|-}}), 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.<ref name="Alscher"/><ref name="Smirnoff"/><ref name="Raychaudhuri"/>

=== Bacteria ===

Human white blood cells use enzymes such as [[NADPH oxidase]] to 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.<ref name="pmid21659326">{{cite journal | vauthors = Vanaporn M, Wand M, Michell SL, Sarkar-Tyson M, Ireland P, Goldman S, Kewcharoenwong C, Rinchai D, Lertmemongkolchai G, Titball RW | display-authors = 6 | title = Superoxide dismutase C is required for intracellular survival and virulence of Burkholderia pseudomallei | journal = Microbiology | volume = 157 | issue = Pt 8 | pages = 2392–2400 | date = August 2011 | pmid = 21659326 | doi = 10.1099/mic.0.050823-0 | doi-access = free }}</ref>