Editing Ferredoxin

{{Short description|Iron–sulfur proteins that mediate electron transfer in metabolic reactions}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
'''Ferredoxins''' (from [[Latin]] ''ferrum'': [[iron]] + [[redox]], often abbreviated "fd") are [[iron–sulfur protein]]s that mediate [[electron transfer]] in a range of metabolic reactions. The term "ferredoxin" was coined by D.C. Wharton of the [[DuPont]] Co. and applied to the "iron protein" first purified in 1962 by Mortenson, Valentine, and Carnahan from the [[anaerobic organism|anaerobic]] bacterium ''[[Clostridium pasteurianum]]''.<ref name="pmid14476372">{{cite journal | vauthors = Mortenson LE, Valentine RC, Carnahan JE | title = An electron transport factor from Clostridium pasteurianum | journal = Biochemical and Biophysical Research Communications | volume = 7 | issue = 6 | pages = 448–52 | date = June 1962 | pmid = 14476372 | doi = 10.1016/0006-291X(62)90333-9 }}</ref><ref name="pmid14244728">{{cite journal | vauthors = Valentine RC | title = Bacterial Ferredoxin | journal = Bacteriological Reviews | volume = 28 | issue = 4 | pages = 497–517 | date = December 1964 | pmid = 14244728 | pmc = 441251 | doi = 10.1128/MMBR.28.4.497-517.1964 }}</ref>

Another redox protein, isolated from spinach [[chloroplast]]s, was termed "chloroplast ferredoxin".<ref name="pmid14039612">{{cite journal | vauthors = Tagawa K, Arnon DI | title = Ferredoxins as electron carriers in photosynthesis and in the biological production and consumption of hydrogen gas | journal = Nature | volume = 195 | issue = 4841 | pages = 537–43 | date = August 1962 | pmid = 14039612 | doi = 10.1038/195537a0 | s2cid = 4213017 | bibcode = 1962Natur.195..537T }}</ref> The chloroplast ferredoxin is involved in both cyclic and non-cyclic [[photophosphorylation]] reactions of [[photosynthesis]]. In non-cyclic photophosphorylation, ferredoxin is the last electron acceptor thus reducing the enzyme NADP<sup>+</sup> reductase.  It accepts electrons produced from [[sunlight]]-[[Electron excitation|excited]] [[chlorophyll]] and transfers them to the enzyme ferredoxin: NADP<sup>+</sup> oxidoreductase {{EC number|1.18.1.2}}.

Ferredoxins are small proteins containing [[iron]] and [[sulfur]] atoms organized as [[iron–sulfur cluster]]s. These biological "[[capacitors]]" can accept or discharge electrons, with the effect of a change in the oxidation state of the iron atoms between +2 and +3. In this way, ferredoxin acts as an electron transfer agent in biological [[redox]] reactions.

Other [[bioinorganic]] electron transport systems include [[rubredoxin]]s, [[cytochromes]], [[blue copper protein]]s, and the structurally related [[Rieske protein]]s.

Ferredoxins can be classified according to the nature of their iron–sulfur clusters and by sequence similarity.

== Bioenergetics of ferredoxins ==
Ferredoxins typically carry out a single electron transfer.

: {{chem|Fd|ox|''0''}} + {{e-}} <chem><=></chem> {{chem|Fd|red|-}}

However a few bacterial ferredoxins (of the 2[4Fe4S] type) have two iron sulfur clusters and can carry out two electron transfer reactions. Depending on the sequence of the protein, the two transfers can have nearly identical reduction potentials or they may be significantly different.<ref name="MaioccoArcinas2019">{{cite journal | vauthors = Maiocco SJ, Arcinas AJ, Booker SJ, Elliott SJ | title = Parsing redox potentials of five ferredoxins found within Thermotoga maritima | journal = Protein Science | volume = 28 | issue = 1 | pages = 257–266 | date = January 2019 | pmid = 30418685 | doi = 10.1002/pro.3547 | pmc = 6295886 | doi-access = free }}</ref><ref name="Gao-SheridanPershad1998">{{cite journal | vauthors = Gao-Sheridan HS, Pershad HR, Armstrong FA, Burgess BK | title = Discovery of a novel ferredoxin from Azotobacter vinelandii containing two [4Fe-4S] clusters with widely differing and very negative reduction potentials | journal = The Journal of Biological Chemistry | volume = 273 | issue = 10 | pages = 5514–9 | date = March 1998 | pmid = 9488675 | doi = 10.1074/jbc.273.10.5514 | doi-access = free }}</ref>

: {{chem|Fd|ox|''0''}} + {{e-}} <chem><=></chem> {{chem|Fd|red|-}}

: {{chem|Fd|red|-}} + {{e-}} <chem><=></chem> {{chem|Fd|red|2-}}

Ferredoxins are one of the most reducing biological electron carriers. They typically have a [[reduction potential|mid point potential]] of -420 mV.<ref name=Buckel2018>{{cite journal | vauthors = Buckel W, Thauer RK | title = Flavin-Based Electron Bifurcation, Ferredoxin, Flavodoxin, and Anaerobic Respiration With Protons (Ech) or NAD<sup>+</sup> (Rnf) as Electron Acceptors: A Historical Review | journal = Frontiers in Microbiology | volume = 9 | pages = 401 | year = 2018 | pmid = 29593673 | pmc = 5861303 | doi = 10.3389/fmicb.2018.00401 | doi-access = free }}</ref> The reduction potential of a substance in the cell will differ from its midpoint potential depending on the concentrations of its reduced and oxidized forms. For a one electron reaction, the potential changes by [[Nernst equation|around 60 mV]] for each power of ten change in the ratio of the concentration. For example, if the ferredoxin pool is around 95% reduced, the reduction potential will be around -500 mV.<ref name=Huwiler2019>{{cite journal | vauthors = Huwiler SG, Löffler C, Anselmann SE, Stärk HJ, von Bergen M, Flechsler J, Rachel R, Boll M | title = One-megadalton metalloenzyme complex in ''Geobacter metallireducens'' involved in benzene ring reduction beyond the biological redox window | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 6 | pages = 2259–2264 | date = February 2019 | pmid = 30674680 | pmc = 6369795 | doi = 10.1073/pnas.1819636116 | bibcode = 2019PNAS..116.2259H | doi-access = free }}</ref> In comparison, [[Table of standard reduction potentials for half-reactions important in biochemistry|other biological reactions]] mostly have less reducing potentials: for example the primary biosynthetic reductant of the cell, [[NADPH]] has a cellular redox potential of -370 mV ({{chem|E|0}} = -320 mV).

Depending on the sequence of the supporting protein ferredoxins have  reduction potential from around -500 mV<ref name=Buckel2018/><ref name=Li2016>{{cite journal | doi = 10.1016/j.electacta.2016.02.119 | title = The Catalytic Bias of 2-Oxoacid:ferredoxin Oxidoreductase in CO2: Evolution and reduction through a ferredoxin-mediated electrocatalytic assay | year = 2016 | vauthors = Li B, Elliott SJ | journal = Electrochimica Acta | volume = 199 | pages = 349–356 | doi-access =free  }}</ref> to -340 mV.<ref name=Thamer2003>{{cite journal | vauthors = Thamer W, Cirpus I, Hans M, Pierik AJ, Selmer T, Bill E, Linder D, Buckel W | title = A two [4Fe-4S]-cluster-containing ferredoxin as an alternative electron donor for 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans | journal = Archives of Microbiology | volume = 179 | issue = 3 | pages = 197–204 | date = March 2003 | pmid = 12610725 | doi = 10.1007/s00203-003-0517-8 | bibcode = 2003ArMic.179..197T | s2cid = 23621034 }}</ref> A single cell can have multiple types of ferredoxins where each type is tuned to optimally carry out different reactions.<ref name=Hanke2004/>

=== Reduction of ferredoxin ===
The highly reducing ferredoxins are reduced either by using another strong reducing agent, or by using some source of energy to "boost" electrons from less reducing sources to the ferredoxin.<ref name="BoydAmenabar2020">{{cite journal | vauthors = Boyd ES, Amenabar MJ, Poudel S, Templeton AS | title = Bioenergetic constraints on the origin of autotrophic metabolism | journal = Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences | volume = 378 | issue = 2165 | pages = 20190151 | date = February 2020 | pmid = 31902344 | doi = 10.1098/rsta.2019.0151 | pmc = 7015307 | bibcode = 2020RSPTA.37890151B | doi-access = free }}</ref>

==== Direct reduction ====
Reactions that reduce Fd include the oxidation of aldehydes to acids like the [[Glyceraldehyde-3-phosphate dehydrogenase (ferredoxin)|glyceraldehyde to glycerate]] reaction (-580 mV), the [[carbon monoxide dehydrogenase]] reaction (-520 mV), and the 2-oxoacid:Fd Oxidoreductase reactions (-500 mV)<ref name=Gibson2016>{{cite journal | vauthors = Gibson MI, Chen PY, Drennan CL | title = A structural phylogeny for understanding 2-oxoacid oxidoreductase function | journal = Current Opinion in Structural Biology | volume = 41 | pages = 54–61 | date = December 2016 | pmid = 27315560 | pmc = 5381805 | doi = 10.1016/j.sbi.2016.05.011 }}</ref><ref name=Li2016/> like the reaction carried out by [[pyruvate synthase]].<ref name=Huwiler2019/>

==== Membrane potential coupled reduction ====
Ferredoxin can also be reduced by using NADH (-320 mV) or {{chem|H|2}} (-414 mV), but these processes are coupled to the consumption of the [[membrane potential]] to power the "boosting" of electrons to the higher energy state.<ref name=Buckel2018/> The [[Rnf complex]] is a widespread membrane protein in [[bacteria]] that [[Reversible reaction|reversibly]] [[Electron transfer|transfers electrons]] between NADH and ferredoxin while pumping {{chem|Na|+}} or {{chem|H|+}} ions across the [[cell membrane]]. The [[chemiosmotic potential]] of the membrane is consumed to power the unfavorable reduction of {{chem|Fd|ox}} by NADH. This reaction is an essential source of {{chem|Fd|-|red}} in many [[autotroph]]ic organisms. If the [[Cell (biology)|cell]] is growing on [[Substrate (biology)|substrates]] that provide excess {{chem|Fd|-|red}}, the Rnf complex can transfer these electrons to {{chem|NAD|+}} and store the resultant energy in the membrane potential.<ref name="WestphalWiechmann2018">{{cite journal | vauthors = Westphal L, Wiechmann A, Baker J, Minton NP, Müller V | title = The Rnf Complex is an Energy-Coupled Transhydrogenase Essential to Reversibly Link Cellular NADH and Ferredoxin Pools in the Acetogen Acetobacterium woodii | journal = Journal of Bacteriology | volume = 200 | issue = 21 | date = November 2018 | pmid = 30126940 | doi = 10.1128/JB.00357-18 | pmc = 6182241 | doi-access = free }}</ref> The energy converting [[hydrogenase]]s (Ech) are a family of [[enzyme]]s that reversibly couple the transfer of electrons between {{chem|Fd}} and {{chem|H|2}} while pumping {{chem|H|+}} ions across the membrane to balance the energy difference.<ref name="SchoelmerichMüller2019">{{cite journal | vauthors = Schoelmerich MC, Müller V | title = Energy-converting hydrogenases: the link between H<sub>2</sub> metabolism and energy conservation | journal = Cellular and Molecular Life Sciences | volume = 77 | issue = 8 | pages = 1461–1481 | date = April 2020 | pmid = 31630229 | doi = 10.1007/s00018-019-03329-5 | s2cid = 204786346 | pmc = 11636919 }}</ref>

: {{chem|Fd|ox|''0''}} + {{chem|NADH}} + {{chem|Na|outside|+}} <chem><=></chem> {{chem|Fd|red|2-}} + {{chem| NAD|+}} + {{chem|Na|inside|+}}

: {{chem|Fd|ox|''0''}} + {{chem|H|2}} + {{chem|H|outside|+}} <chem><=></chem> {{chem|Fd|red|2-}} + {{chem| H|+}} + {{chem|H|inside|+}}

==== Electron bifurcation ====
The unfavourable reduction of Fd from a less reducing [[electron donor]] can be coupled simultaneously with the favourable reduction of an [[oxidizing agent]] through an [[electron bifurcation]] reaction.<ref name=Buckel2018/> An example of the electron bifurcation reaction is the generation of {{chem|Fd|red|-}} for [[nitrogen fixation]] in certain [[Aerobic organism|aerobic]] [[diazotroph]]s. Typically, in [[oxidative phosphorylation]] the transfer of electrons from [[NADH]] to [[ubiquinone]] (Q) is coupled to charging the proton motive force. In ''[[Azotobacter]]'' the energy released by transferring one electron from NADH to Q is used to simultaneously boost the transfer of one electron from NADH to Fd.<ref name=Ledbetter2017>{{cite journal | vauthors = Ledbetter RN, Garcia Costas AM, Lubner CE, Mulder DW, Tokmina-Lukaszewska M, Artz JH, Patterson A, Magnuson TS, Jay ZJ, Duan HD, Miller J, Plunkett MH, Hoben JP, Barney BM, Carlson RP, Miller AF, Bothner B, King PW, Peters JW, Seefeldt LC | title = The Electron Bifurcating FixABCX Protein Complex from Azotobacter vinelandii: Generation of Low-Potential Reducing Equivalents for Nitrogenase Catalysis | journal = Biochemistry | volume = 56 | issue = 32 | pages = 4177–4190 | date = August 2017 | pmid = 28704608 | pmc = 7610252 | doi = 10.1021/acs.biochem.7b00389 }}</ref><ref name="PoudelColman2018">{{cite journal | vauthors = Poudel S, Colman DR, Fixen KR, Ledbetter RN, Zheng Y, Pence N, Seefeldt LC, Peters JW, Harwood CS, Boyd ES | title = Electron Transfer to Nitrogenase in Different Genomic and Metabolic Backgrounds | journal = Journal of Bacteriology | volume = 200 | issue = 10 | date = May 2018 | pmid = 29483165 | doi = 10.1128/JB.00757-17 | pmc = 5915786 | doi-access = free }}</ref>

==== Direct reduction of high potential ferredoxins ====
Some ferredoxins have a sufficiently high [[redox potential]] that they can be directly reduced by NADPH. One such ferredoxin is [[Adrenal ferredoxin|adrenoxin]] (-274 mV) which takes part in the [[biosynthesis]] of many [[mammal]]ian [[steroid]]s.<ref name="EwenRingle2012">{{cite journal | vauthors = Ewen KM, Ringle M, Bernhardt R | title = Adrenodoxin--a versatile ferredoxin | journal = IUBMB Life | volume = 64 | issue = 6 | pages = 506–12 | date = June 2012 | pmid = 22556163 | doi = 10.1002/iub.1029 | doi-access = free }}</ref> The ferredoxin Fd3 in the [[root]]s of plants that reduces [[nitrate]] and [[sulfite]] has a midpoint potential of -337 mV and is also reduced by NADPH.<ref name=Hanke2004>{{cite journal | vauthors = Hanke GT, Kimata-Ariga Y, Taniguchi I, Hase T | title = A post genomic characterization of Arabidopsis ferredoxins | journal = Plant Physiology | volume = 134 | issue = 1 | pages = 255–64 | date = January 2004 | pmid = 14684843 | pmc = 316305 | doi = 10.1104/pp.103.032755 }}</ref>

== Fe<sub>2</sub>S<sub>2</sub> ferredoxins ==
{{Infobox protein family
| Symbol = Fer2 
| Name = 2Fe-2S iron-sulfur cluster binding domain 
| image = Fe2S2.svg
| width = 
| caption = ''Structural representation of an Fe<sub>2</sub>S<sub>2</sub> ferredoxin.''
| Pfam= PF00111
| Pfam_clan=CL0486
| InterPro= IPR001041
| SMART= 
| Prosite = PDOC00642
| SCOP = 3fxc
| TCDB = 
| OPM family= 
| OPM protein= 1kf6
}}

Members of the 2Fe–2S ferredoxin superfamily ({{InterPro|IPR036010}}) have a general core structure consisting of beta(2)-alpha-beta(2), which includes putidaredoxin, terpredoxin, and adrenodoxin.<ref name="PUB00016347">{{cite journal | vauthors = Armengaud J, Sainz G, Jouanneau Y, Sieker LC | title = Crystallization and preliminary X-ray diffraction analysis of a [2Fe-2S] ferredoxin (FdVI) from Rhodobacter capsulatus | journal = Acta Crystallographica. Section D, Biological Crystallography | volume = 57 | issue = Pt 2 | pages = 301–3 | date = February 2001 | pmid = 11173487 | doi = 10.1107/S0907444900017832 }}</ref><ref name="PUB00016348">{{cite journal | vauthors = Sevrioukova IF | title = Redox-dependent structural reorganization in putidaredoxin, a vertebrate-type [2Fe-2S] ferredoxin from Pseudomonas putida | journal = Journal of Molecular Biology | volume = 347 | issue = 3 | pages = 607–21 | date = April 2005 | pmid = 15755454 | doi = 10.1016/j.jmb.2005.01.047 }}</ref><ref name="PUB00016349">{{cite journal | vauthors = Mo H, Pochapsky SS, Pochapsky TC | title = A model for the solution structure of oxidized terpredoxin, a Fe2S2 ferredoxin from Pseudomonas | journal = Biochemistry | volume = 38 | issue = 17 | pages = 5666–75 | date = April 1999 | pmid = 10220356 | doi = 10.1021/bi983063r | citeseerx = 10.1.1.34.4745 }}</ref><ref name="PUB00016350">{{cite journal | vauthors = Beilke D, Weiss R, Löhr F, Pristovsek P, Hannemann F, Bernhardt R, Rüterjans H | title = A new electron transport mechanism in mitochondrial steroid hydroxylase systems based on structural changes upon the reduction of adrenodoxin | journal = Biochemistry | volume = 41 | issue = 25 | pages = 7969–78 | date = June 2002 | pmid = 12069587 | doi = 10.1021/bi0160361 }}</ref> They are proteins of around one hundred amino acids with four conserved cysteine residues to which the 2Fe–2S cluster is ligated. This conserved region is also found as a domain in various metabolic enzymes and in multidomain proteins, such as aldehyde oxidoreductase (''N''-terminal), xanthine oxidase (''N''-terminal), phthalate dioxygenase reductase (''C''-terminal), succinate dehydrogenase iron–sulphur protein (''N''-terminal), and methane monooxygenase reductase (''N''-terminal).

=== Plant-type ferredoxins ===
One group of ferredoxins, originally found in [[chloroplast]] membranes, has been termed "chloroplast-type" or "plant-type" ({{InterPro|IPR010241}}). Its active center is a [Fe<sub>2</sub>S<sub>2</sub>] cluster, where the iron atoms are tetrahedrally coordinated both by inorganic sulfur atoms and by sulfurs of four conserved [[cysteine]] (Cys) residues.

In chloroplasts, Fe<sub>2</sub>S<sub>2</sub> ferredoxins function as electron carriers in the [[Photophosphorylation|photosynthetic electron transport chain]] and as electron donors to various cellular proteins, such as glutamate synthase, nitrite reductase, sulfite reductase, and the [[Magnesium-protoporphyrin IX monomethyl ester (oxidative) cyclase|cyclase of chlorophyll biosynthesis]].<ref>{{cite journal | vauthors = Stuart D, Sandström M, Youssef HM, Zakhrabekova S, Jensen PE, Bollivar DW, Hansson M | title = Aerobic Barley Mg-protoporphyrin IX Monomethyl Ester Cyclase is Powered by Electrons from Ferredoxin | journal = Plants | volume = 9 | issue = 9 | pages = 1157 | date = September 2020 | pmid = 32911631 | doi = 10.3390/plants9091157 | pmc = 7570240 | doi-access = free }}</ref> Since the cyclase is a ferredoxin dependent enzyme this may provide a mechanism for coordination between photosynthesis and the chloroplasts need for chlorophyll by linking chlorophyll biosynthesis to the photosynthetic electron transport chain. In hydroxylating bacterial dioxygenase systems, they serve as intermediate electron-transfer carriers between reductase flavoproteins and oxygenase.

=== Thioredoxin-like ferredoxins ===
The Fe<sub>2</sub>S<sub>2</sub> ferredoxin from ''Clostridium pasteurianum'' (''Cp''2FeFd; {{UniProt|P07324}}) has been recognized as distinct protein family on the basis of its amino acid sequence, spectroscopic properties of its iron–sulfur cluster and the unique ligand swapping ability of two cysteine ligands to the [Fe<sub>2</sub>S<sub>2</sub>] cluster. Although the physiological role of this ferredoxin remains unclear, a strong and specific interaction of ''Cp''2FeFd with the molybdenum-iron protein of [[nitrogenase]] has been revealed. Homologous ferredoxins from ''[[Azotobacter vinelandii]]'' (''Av''2FeFdI; {{UniProt|P82802}}) and ''Aquifex aeolicus'' (''Aa''Fd; {{UniProt|O66511}}) have been characterized. The crystal structure of ''Aa''Fd has been solved. ''Aa''Fd exists as a dimer. The structure of ''Aa''Fd monomer is different from other Fe<sub>2</sub>S<sub>2</sub> ferredoxins. The fold belongs to the α+β class, with first four β-strands and two α-helices adopting a variant of the [[thioredoxin]] fold.<ref>{{cite journal | vauthors = Yeh AP, Ambroggio XI, Andrade SL, Einsle O, Chatelet C, Meyer J, Rees DC | title = High resolution crystal structures of the wild type and Cys-55→Ser and Cys-59→Ser variants of the thioredoxin-like [2Fe-2S] ferredoxin from Aquifex aeolicus | journal = The Journal of Biological Chemistry | volume = 277 | issue = 37 | pages = 34499–507 | date = September 2002 | pmid = 12089152 | doi = 10.1074/jbc.M205096200 | doi-access = free }}</ref> [[UniProt]] categorizes these as the "2Fe2S Shethna-type ferredoxin" family.<ref>[https://www.uniprot.org/uniprot/?query=family:%222Fe2S+Shethna-type+ferredoxin+family%22&sort=score family:"2fe2s shethna type ferredoxin family"]</ref>

=== Adrenodoxin-type ferredoxins ===
{{infobox protein
| Name = [[FDX1|ferredoxin 1]]
| caption = Crystal structure of human ferredoxin-1 (FDX1).<ref name="Chaikuad_2010">{{PDB|3P1M}}; {{cite journal | vauthors = Chaikuad A, Johansson, C, Krojer, T, Yue, WW, Phillips, C, Bray, JE, Pike, ACW, Muniz, JRC, Vollmar, M, Weigelt, J, Arrowsmith, CH, Edwards, AM, Bountra, C, Kavanagh, K, Oppermann, U | title = Crystal structure of human ferredoxin-1 (FDX1) in complex with iron-sulfur cluster | journal = Worldwide Protein Data Bank | year=2010 | doi = 10.2210/pdb3p1m/pdb }}</ref>
| image = 3P1M.pdb1.png
| width = 
| HGNCid = 3638
| Symbol = [[FDX1]]
| AltSymbols = FDX
| EntrezGene = 2230
| OMIM = 103260
| RefSeq = NM_004109
| UniProt = P10109
| PDB = 
| ECnumber = 
| Chromosome = 11
| Arm = q
| Band = 22.3
| LocusSupplementaryData = 
}}
[[Adrenodoxin]] (adrenal ferredoxin; {{InterPro|IPR001055}}), putidaredoxin, and terpredoxin make up a family of soluble Fe<sub>2</sub>S<sub>2</sub> proteins that act as single electron carriers, mainly found in [[eukaryotic]] mitochondria and [[Pseudomonadota]]. The human variant of adrenodoxin is referred to as ferredoxin-1 and [[FDX1L|ferredoxin-2]]. In mitochondrial monooxygenase systems, adrenodoxin transfers an electron from [[Ferredoxin-NADP+ reductase|NADPH:adrenodoxin reductase]] to membrane-bound [[cytochrome P450]]. In bacteria, putidaredoxin and terpredoxin transfer electrons between corresponding NADH-dependent ferredoxin reductases and soluble P450s.<ref name="pmid2180940">{{cite journal | vauthors = Peterson JA, Lorence MC, Amarneh B | title = Putidaredoxin reductase and putidaredoxin. Cloning, sequence determination, and heterologous expression of the proteins | journal = The Journal of Biological Chemistry | volume = 265 | issue = 11 | pages = 6066–73 | date = April 1990 | doi = 10.1016/S0021-9258(19)39292-0 | pmid = 2180940 | doi-access = free }}</ref><ref name="pmid1629218">{{cite journal | vauthors = Peterson JA, Lu JY, Geisselsoder J, Graham-Lorence S, Carmona C, Witney F, Lorence MC | title = Cytochrome P-450terp. Isolation and purification of the protein and cloning and sequencing of its operon | journal = The Journal of Biological Chemistry | volume = 267 | issue = 20 | pages = 14193–203 | date = July 1992 | doi = 10.1016/S0021-9258(19)49697-X | pmid = 1629218 | doi-access = free }}</ref> The exact functions of other members of this family are not known, although ''Escherichia coli'' Fdx is shown to be involved in biogenesis of Fe–S clusters.<ref>{{cite journal | vauthors = Tokumoto U, Takahashi Y | title = Genetic analysis of the isc operon in Escherichia coli involved in the biogenesis of cellular iron-sulfur proteins | journal = Journal of Biochemistry | volume = 130 | issue = 1 | pages = 63–71 | date = July 2001 | pmid = 11432781 | doi = 10.1093/oxfordjournals.jbchem.a002963 }}</ref> Despite low sequence similarity between adrenodoxin-type and plant-type ferredoxins, the two classes have a similar folding topology.

Ferredoxin-1 in humans participates in the synthesis of thyroid hormones. It also transfers electrons from adrenodoxin reductase to [[CYP11A1]], a CYP450 enzyme responsible for cholesterol side chain cleavage. FDX-1 has the capability to bind to metals and proteins.<ref name="entrez-fdx1">{{cite web | title = Entrez Gene: FDX1 ferredoxin 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2230}}</ref> Ferredoxin-2 participates in heme A and iron–sulphur protein synthesis.<ref>{{cite web |title=FDX2 ferredoxin 2 [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/112812 |website=www.ncbi.nlm.nih.gov |access-date=8 April 2019}}</ref>

== Fe<sub>4</sub>S<sub>4</sub> and Fe<sub>3</sub>S<sub>4</sub> ferredoxins ==

The [Fe<sub>4</sub>S<sub>4</sub>] ferredoxins may be further subdivided into low-potential (bacterial-type) and [[HIPIP|high-potential (HiPIP) ferredoxins]].

Low- and high-potential ferredoxins are related by the following redox scheme:

[[Image:FdRedox.png|center|500px]]

The formal oxidation numbers of the iron ions can be [2Fe<sup>3+</sup>, 2Fe<sup>2+</sup>] or [1Fe<sup>3+</sup>, 3Fe<sup>2+</sup>] in low-potential ferredoxins. The oxidation numbers of the iron ions in high-potential ferredoxins can be [3Fe<sup>3+</sup>, 1Fe<sup>2+</sup>] or [2Fe<sup>3+</sup>, 2Fe<sup>2+</sup>].

=== Bacterial-type ferredoxins ===
{{Infobox protein family
| Symbol = Fer4 
| Name = 3Fe-4S binding domain 
| image = Fe3S4.svg
| width = 
| caption = ''Structural representation of an Fe<sub>3</sub>S<sub>4</sub> ferredoxin.''
| Pfam= PF00037
| InterPro= IPR001450
| SMART= 
| Prosite = PDOC00176
| SCOP = 5fd1
| TCDB = 
| OPM family= 
| OPM protein= 1kqf
| PDB= 
{{PDB3|1h98}}A:33-56     {{PDB3|1bd6}} :33-56     {{PDB3|1bwe}}A:33-56     
{{PDB3|1bqx}}A:33-56     {{PDB3|1bc6}} :33-56     {{PDB3|7fd1}}A:33-56     
{{PDB3|6fd1}} :33-56     {{PDB3|6fdr}}A:33-56     {{PDB3|1frx}} :33-56     
{{PDB3|1gao}}B:33-56     {{PDB3|1b0t}}A:33-56     {{PDB3|1b0v}}A:33-56     
{{PDB3|1fd2}} :33-56     {{PDB3|1fdd}} :33-56     {{PDB3|1fer}} :33-56     
{{PDB3|1axq}} :33-56     {{PDB3|1g6b}}A:33-56     {{PDB3|2fd2}} :33-56     
{{PDB3|1ff2}}A:33-56     {{PDB3|1pc5}}A:33-56     {{PDB3|7fdr}}A:33-56     
{{PDB3|1g3o}}A:33-56     {{PDB3|1ftc}}A:33-56     {{PDB3|1frm}} :33-56     
{{PDB3|5fd1}} :33-56     {{PDB3|1a6l}} :33-56     {{PDB3|1frj}} :33-56     
{{PDB3|1fdb}} :33-56     {{PDB3|1fri}} :33-56     {{PDB3|1pc4}}A:33-56     
{{PDB3|1f5b}}A:33-56     {{PDB3|1frh}} :33-56     {{PDB3|1d3w}}A:33-56     
{{PDB3|1frk}} :33-56     {{PDB3|1f5c}}A:33-56     {{PDB3|1frl}} :33-56     
{{PDB3|1fda}} :33-56     {{PDB3|1clf}} :31-54     {{PDB3|1dur}}A:28-51     
{{PDB3|1fca}} :30-53     {{PDB3|1fdn}} :30-53     {{PDB3|2fdn}} :30-53     
{{PDB3|1xer}} :77-100    {{PDB3|1h7x}}A:946-969   {{PDB3|1gte}}A:946-969   
{{PDB3|1h7w}}B:946-969   {{PDB3|1gth}}A:946-969   {{PDB3|1gt8}}A:946-969   
{{PDB3|1gx7}}A:28-51     {{PDB3|1hfe}}L:28-51     {{PDB3|1blu}} :2-25      
{{PDB3|1rgv}}A:2-25      {{PDB3|1kqf}}B:126-149   {{PDB3|1kqg}}B:126-149   
{{PDB3|1jb0}}C:4-27      {{PDB3|1k0t}}A:4-27      {{PDB3|1rof}} :3-26      
{{PDB3|1vjw}} :3-26      {{PDB3|1dwl}}A:2-25      {{PDB3|2pda}}A:738-763   
{{PDB3|1b0p}}A:738-763   {{PDB3|1kek}}A:738-763   {{PDB3|1c4c}}A:183-206   
{{PDB3|1c4a}}A:183-206   {{PDB3|1feh}}A:183-206   {{PDB3|1l0v}}N:142-165   
{{PDB3|1kfy}}N:142-165   {{PDB3|1kf6}}B:142-165   {{PDB3|1jnr}}B:40-63     
{{PDB3|1jnz}}B:40-63     
}} 
A group of Fe<sub>4</sub>S<sub>4</sub> ferredoxins, originally found in bacteria, has been termed "bacterial-type". Bacterial-type ferredoxins may in turn be subdivided into further groups, based on their sequence properties. Most contain at least one conserved domain, including four cysteine residues that bind to a [Fe<sub>4</sub>S<sub>4</sub>] cluster. In ''Pyrococcus furiosus'' Fe<sub>4</sub>S<sub>4</sub> ferredoxin, one of the conserved Cys residues is substituted with aspartic acid.

During the evolution of bacterial-type ferredoxins, intrasequence gene duplication, transposition and fusion events occurred, resulting in the appearance of proteins with multiple iron–sulfur centers. In some bacterial ferredoxins, one of the duplicated domains has lost one or more of the four conserved Cys residues. These domains have either lost their iron–sulfur binding property or bind to a [Fe<sub>3</sub>S<sub>4</sub>] cluster instead of a [Fe<sub>4</sub>S<sub>4</sub>] cluster<ref name="PUB00003253">{{cite journal | vauthors = Fukuyama K, Matsubara H, Tsukihara T, Katsube Y | title = Structure of [4Fe-4S] ferredoxin from Bacillus thermoproteolyticus refined at 2.3 A resolution. Structural comparisons of bacterial ferredoxins | journal = Journal of Molecular Biology | volume = 210 | issue = 2 | pages = 383–98 | date = November 1989 | pmid = 2600971 | doi = 10.1016/0022-2836(89)90338-0 }}</ref> and dicluster-type.<ref name="PUB00003332">{{cite journal | vauthors = Duée ED, Fanchon E, Vicat J, Sieker LC, Meyer J, Moulis JM | title = Refined crystal structure of the 2[4Fe-4S] ferredoxin from Clostridium acidurici at 1.84 A resolution | journal = Journal of Molecular Biology | volume = 243 | issue = 4 | pages = 683–95 | date = November 1994 | pmid = 7966291 | doi = 10.1016/0022-2836(94)90041-8 }}</ref>

3-D structures are known for a number of monocluster and dicluster bacterial-type ferredoxins. The fold belongs to the α+β class, with 2-7 α-helices and four β-strands forming a barrel-like structure, and an extruded loop containing three "proximal" Cys ligands of the iron–sulfur cluster.

=== High-potential iron–sulfur proteins ===
[[High potential iron–sulfur protein]]s (HiPIPs) form a unique family of Fe<sub>4</sub>S<sub>4</sub> ferredoxins that function in anaerobic electron transport chains. Some HiPIPs have a redox potential higher than any other known iron–sulfur protein (e.g., HiPIP from ''[[Rhodopila globiformis]]'' has a redox potential of ca. -450 mV). Several HiPIPs have so far been characterized structurally, their folds belonging to the α+β class. As in other bacterial ferredoxins, the [Fe<sub>4</sub>S<sub>4</sub>] unit forms a [[cubane-type cluster]] and is ligated to the protein ''via'' four Cys residues.

== Human proteins from ferredoxin family ==
* 2Fe–2S: [[AOX1]];      [[FDX1]];      [[FDX2]];     [[NDUFS1]];    [[SDHB]];      [[Xanthine dehydrogenase|XDH]];
* 4Fe–4S: [[ABCE1]];     [[DPYD]];      [[NDUFS8]];

== References ==
{{reflist|32em}}

== Further reading ==
{{refbegin|32em}}
* {{cite journal | vauthors = Bruschi M, Guerlesquin F | title = Structure, function and evolution of bacterial ferredoxins | journal = FEMS Microbiology Reviews | volume = 4 | issue = 2 | pages = 155–75 | year = 1988 | pmid = 3078742 | doi = 10.1111/j.1574-6968.1988.tb02741.x | doi-access = free }}
* {{cite journal | vauthors = Ciurli S, Musiani F | title = High potential iron-sulfur proteins and their role as soluble electron carriers in bacterial photosynthesis: tale of a discovery | journal = Photosynthesis Research | volume = 85 | issue = 1 | pages = 115–31 | year = 2005 | pmid = 15977063 | doi = 10.1007/s11120-004-6556-4 | bibcode = 2005PhoRe..85..115C | s2cid = 27768048 }}
* {{cite journal | vauthors = Fukuyama K | title = Structure and function of plant-type ferredoxins | journal = Photosynthesis Research | volume = 81 | issue = 3 | pages = 289–301 | year = 2004 | pmid = 16034533 | doi = 10.1023/B:PRES.0000036882.19322.0a | bibcode = 2004PhoRe..81..289F | s2cid = 24574958 }}
* {{cite journal | vauthors = Grinberg AV, Hannemann F, Schiffler B, Müller J, Heinemann U, Bernhardt R | title = Adrenodoxin: structure, stability, and electron transfer properties | journal = Proteins | volume = 40 | issue = 4 | pages = 590–612 | date = September 2000 | pmid = 10899784 | doi = 10.1002/1097-0134(20000901)40:4<590::AID-PROT50>3.0.CO;2-P | s2cid = 113757 }}
* {{cite journal | vauthors = Holden HM, Jacobson BL, Hurley JK, Tollin G, Oh BH, Skjeldal L, Chae YK, Cheng H, Xia B, Markley JL | title = Structure-function studies of [2Fe-2S] ferredoxins | journal = Journal of Bioenergetics and Biomembranes | volume = 26 | issue = 1 | pages = 67–88 | date = February 1994 | pmid = 8027024 | doi = 10.1007/BF00763220 | s2cid = 12560221 }}
* {{cite journal | vauthors = Meyer J | title = Ferredoxins of the third kind | journal = FEBS Letters | volume = 509 | issue = 1 | pages = 1–5 | date = November 2001 | pmid = 11734195 | doi = 10.1016/S0014-5793(01)03049-6 | s2cid = 8101608 | doi-access = free | bibcode = 2001FEBSL.509....1M }}
{{refend}}

== External links ==
* {{InterPro|IPR006057}} - 2Fe–2S ferredoxin subdomain
* {{InterPro|IPR001055}} - Adrenodoxin
* {{InterPro|IPR001450}} - 4Fe–4S ferredoxin, iron–sulfur binding
* {{InterPro|IPR000170}} - High potential iron–sulfur protein
* {{PDB|1F37}} - X-ray structure of thioredoxin-like ferredoxin from ''Aquifex aeolicus'' (''Aa''Fd)

{{Portal|Biology}}
{{Authority control}}

[[Category:Iron–sulfur proteins]]
[[Category:Photosynthesis]]
[[Category:Steroid hormone biosynthesis]]