Ferredoxin

Ferredoxins typically carry out a single electron transfer.

: {{chem|Fd|ox|0}} + {{e-}} <=> {{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.{{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 }}{{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 }}

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

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

Ferredoxins are one of the most reducing biological electron carriers. They typically have a mid point potential of -420 mV.{{cite journal | vauthors = Buckel W, Thauer RK | title = Flavin-Based Electron Bifurcation, Ferredoxin, Flavodoxin, and Anaerobic Respiration With Protons (Ech) or NAD⁺ (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 }} 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 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.{{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 }} In comparison, 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{{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 }} to -340 mV.{{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 }} A single cell can have multiple types of ferredoxins where each type is tuned to optimally carry out different reactions.

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.{{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 }}

Reactions that reduce Fd include the oxidation of aldehydes to acids like the glyceraldehyde to glycerate reaction (-580 mV), the carbon monoxide dehydrogenase reaction (-520 mV), and the 2-oxoacid:Fd Oxidoreductase reactions (-500 mV){{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 }} like the reaction carried out by pyruvate synthase.

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. The Rnf complex is a widespread membrane protein in bacteria that reversibly 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 autotrophic organisms. If the cell is growing on 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.{{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 }} The energy converting hydrogenases (Ech) are a family of enzymes 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.{{cite journal | vauthors = Schoelmerich MC, Müller V | title = Energy-converting hydrogenases: the link between H₂ 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 }}

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

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

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. An example of the electron bifurcation reaction is the generation of {{chem|Fd|red|-}} for nitrogen fixation in certain aerobic diazotrophs. 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.{{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 }}{{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 }}

Some ferredoxins have a sufficiently high redox potential that they can be directly reduced by NADPH. One such ferredoxin is adrenoxin (-274 mV) which takes part in the biosynthesis of many mammalian steroids.{{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 }} The ferredoxin Fd3 in the roots of plants that reduces nitrate and sulfite has a midpoint potential of -337 mV and is also reduced by NADPH.{{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 }}

{{Pfam_box

| Symbol = Fer2

| Name = 2Fe-2S iron-sulfur cluster binding domain

| image = Fe2S2.svg

| width =

| caption = Structural representation of an Fe₂S₂ 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.{{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 }}{{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 }}{{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 }}{{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 }} 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).

One group of ferredoxins, originally found in chloroplast membranes, has been termed "chloroplast-type" or "plant-type" ({{InterPro|IPR010241}}). Its active center is a [Fe₂S₂] cluster, where the iron atoms are tetrahedrally coordinated both by inorganic sulfur atoms and by sulfurs of four conserved cysteine (Cys) residues.

In chloroplasts, Fe₂S₂ ferredoxins function as electron carriers in the photosynthetic electron transport chain and as electron donors to various cellular proteins, such as glutamate synthase, nitrite reductase, sulfite reductase, and the cyclase of chlorophyll biosynthesis.{{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 }} 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.

The Fe₂S₂ ferredoxin from Clostridium pasteurianum (Cp2FeFd; {{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 [Fe₂S₂] cluster. Although the physiological role of this ferredoxin remains unclear, a strong and specific interaction of Cp2FeFd with the molybdenum-iron protein of nitrogenase has been revealed. Homologous ferredoxins from Azotobacter vinelandii (Av2FeFdI; {{UniProt|P82802}}) and Aquifex aeolicus (AaFd; {{UniProt|O66511}}) have been characterized. The crystal structure of AaFd has been solved. AaFd exists as a dimer. The structure of AaFd monomer is different from other Fe₂S₂ 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.{{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 }} UniProt categorizes these as the "2Fe2S Shethna-type ferredoxin" family.[https://www.uniprot.org/uniprot/?query=family:%222Fe2S+Shethna-type+ferredoxin+family%22&sort=score family:"2fe2s shethna type ferredoxin family"]

{{infobox protein

| Name = ferredoxin 1

| caption = Crystal structure of human ferredoxin-1 (FDX1).{{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 }}

| 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 Fe₂S₂ 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 ferredoxin-2. In mitochondrial monooxygenase systems, adrenodoxin transfers an electron from NADPH:adrenodoxin reductase to membrane-bound cytochrome P450. In bacteria, putidaredoxin and terpredoxin transfer electrons between corresponding NADH-dependent ferredoxin reductases and soluble P450s.{{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 }}{{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 }} 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.{{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 }} 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.{{cite web | title = Entrez Gene: FDX1 ferredoxin 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2230}} Ferredoxin-2 participates in heme A and iron–sulphur protein synthesis.{{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}}

The [Fe₄S₄] ferredoxins may be further subdivided into low-potential (bacterial-type) and high-potential (HiPIP) ferredoxins.

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

Image:FdRedox.png

The formal oxidation numbers of the iron ions can be [2Fe³⁺, 2Fe²⁺] or [1Fe³⁺, 3Fe²⁺] in low-potential ferredoxins. The oxidation numbers of the iron ions in high-potential ferredoxins can be [3Fe³⁺, 1Fe²⁺] or [2Fe³⁺, 2Fe²⁺].

{{Pfam_box

| Symbol = Fer4

| Name = 3Fe-4S binding domain

| image = Fe3S4.svg

| width =

| caption = Structural representation of an Fe₃S₄ 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 Fe₄S₄ 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 [Fe₄S₄] cluster. In Pyrococcus furiosus Fe₄S₄ 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 [Fe₃S₄] cluster instead of a [Fe₄S₄] cluster{{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 }} and dicluster-type.{{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 }}

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 (HiPIPs) form a unique family of Fe₄S₄ 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 [Fe₄S₄] unit forms a cubane-type cluster and is ligated to the protein via four Cys residues.

• 2Fe–2S: AOX1; FDX1; FDX2; NDUFS1; SDHB; XDH;
• 4Fe–4S: ABCE1; DPYD; NDUFS8;

{{reflist|32em}}

{{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}}

• {{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 (AaFd)

{{Portal|Biology}}

{{Authority control}}

Category:Iron–sulfur proteins

Category:Photosynthesis

Category:Steroid hormone biosynthesis