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266  structures 3695  species 15  interactions 17474  sequences 166  architectures

Family: Fer2 (PF00111)

Summary: 2Fe-2S iron-sulfur cluster binding domain

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This is the Wikipedia entry entitled "Ferredoxin". More...

Ferredoxin Edit Wikipedia article

Ferredoxins (from Latin ferrum: iron + redox, often abbreviated "fd") are iron-sulfur proteins 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 bacterium Clostridium pasteurianum.[1][2]

Another redox protein, isolated from spinach chloroplasts by Tagawa and Arnon in 1962, was termed "chloroplast ferredoxin".[3] 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 and reduces the enzyme NADP+ reductase. It accepts electrons produced from sunlight-excited chlorophyll and transfers them to the enzyme ferredoxin:NADP+ oxidoreductase EC 1.18.1.2.

Ferredoxins are small proteins containing iron and sulfur atoms organized as iron-sulfur clusters. These biological "capacitors" can accept or discharge electrons, the effect being change in the oxidation states (+2 or +3) of the iron atoms. This way, ferredoxin acts as electron transfer agents in biological redox reactions.

Other bioinorganic electron transport systems include rubredoxins, cytochromes, blue copper proteins, and the structurally related Rieske proteins.

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

Fe2S2 ferredoxins[edit]

2Fe-2S iron-sulfur cluster binding domain
Fe2S2.png
Structural representation of an Fe2S2 ferredoxin.
Identifiers
Symbol Fer2
Pfam PF00111
InterPro IPR001041
PROSITE PDOC00642
SCOP 3fxc
SUPERFAMILY 3fxc
OPM protein 1kf6

Members of the 2Fe-2S ferredoxin family have a general core structure consisting of beta(2)-alpha-beta(2), which includes putidaredoxin and terpredoxin, and adrenodoxin.[4][5][6][7] 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[edit]

One group of ferredoxins, originally found in chloroplast membranes, has been termed "chloroplast-type" or "plant-type". The active center is a [Fe2S2] cluster, where the iron atoms are tetrahedrally coordinated both by inorganic sulfur atoms and by sulfurs provided by 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, nitrate reductase and sulfite reductase. In hydroxylating bacterial dioxygenase systems, they serve as intermediate electron-transfer carriers between reductase flavoproteins and oxygenase.

Thioredoxin-like ferredoxins[edit]

The Fe2S2 ferredoxin from Clostridium pasteurianum (Cp2FeFd) 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) and Aquifex aeolicus (AaFd) 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.

Adrenodoxin-type ferredoxins[edit]

ferredoxin 1
3P1M.pdb1.png
Crystal structure of human ferredoxin-1 (FDX1).[8]
Identifiers
Symbol FDX1
Alt. symbols FDX
Entrez 2230
HUGO 3638
OMIM 103260
RefSeq NM_004109
UniProt P10109
Other data
Locus Chr. 11 q22.3

Adrenodoxin (adrenal ferredoxin) is expressed in mammals including humans. The human variant of adrenodoxin is referred to as ferredoxin 1. Adrenodoxin, putidaredoxin, and terpredoxin are soluble Fe2S2 proteins that act as single electron carriers. In mitochondrial monooxygenase systems, adrenodoxin transfers an electron from NADPH:adrenodoxin reductase to membrane-bound cytochrome P450. In bacteria, putidaredoxin and terpredoxin serve as electron carriers between corresponding NADH-dependent ferredoxin reductases and soluble P450s. 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. 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 the cholesterol side chain cleavage cytochrome P450. FDX-1 has the capability to bind to metals and proteins. It can be found within the cellular mitochondrial matrix.

Fe4S4 and Fe3S4 ferredoxins[edit]

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:

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+].

Bacterial-type ferredoxins[edit]

4Fe-4S binding domain
Fe3S4.png
Structural representation of an Fe3S4 ferredoxin.
Identifiers
Symbol Fer4
Pfam PF00037
InterPro IPR001450
PROSITE PDOC00176
SCOP 5fd1
SUPERFAMILY 5fd1
OPM protein 1kqf

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[9] and dicluster-type.[10]

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[edit]

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] cluster adopts a cubane-like conformation and is ligated to the protein via four Cys residues.

Human proteins from ferredoxin family[edit]

References[edit]

  1. ^ Mortenson LE, Valentine RC, Carnahan JE (June 1962). "An electron transport factor from Clostridium pasteurianum". Biochem. Biophys. Res. Commun. 7: 448–52. doi:10.1016/0006-291X(62)90333-9. PMID 14476372. 
  2. ^ Valentine RC (December 1964). "Bacterial ferredoxin". Bacteriol Rev 28: 497–517. PMC 441251. PMID 14244728. 
  3. ^ Tagawa K, Arnon DI (August 1962). "Ferredoxins as electron carriers in photosynthesis and in the biological production and consumption of hydrogen gas". Nature 195 (4841): 537–43. Bibcode:1962Natur.195..537T. doi:10.1038/195537a0. PMID 14039612. 
  4. ^ Jouanneau Y, Armengaud J, Sainz G, Sieker LC (2001). "Crystallization and preliminary X-ray diffraction analysis of a [2Fe-2S] ferredoxin (FdVI) from Rhodobacter capsulatus". Acta Crystallogr. D 57 (Pt 2): 301–303. doi:10.1107/S0907444900017832. PMID 11173487. 
  5. ^ Sevrioukova IF (2005). "Redox-dependent Structural Reorganization in Putidaredoxin, a Vertebrate-type [2Fe-2S] Ferredoxin from Pseudomonas putida". J. Mol. Biol. 347 (3): 607–621. doi:10.1016/j.jmb.2005.01.047. PMID 15755454. 
  6. ^ Pochapsky TC, Mo H, Pochapsky SS (1999). "A model for the solution structure of oxidized terpredoxin, a Fe2S2 ferredoxin from Pseudomonas". Biochemistry 38 (17): 5666–5675. doi:10.1021/bi983063r. PMID 10220356. 
  7. ^ Ruterjans H, Beilke D, Weiss R, Lohr F, Pristovsek P, Hannemann F, Bernhardt R (2002). "A new electron transport mechanism in mitochondrial steroid hydroxylase systems based on structural changes upon the reduction of adrenodoxin". Biochemistry 41 (25): 7969–7978. doi:10.1021/bi0160361. PMID 12069587. 
  8. ^ PDB 3P1M; 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 (2010). "Crystal structure of human ferredoxin-1 (FDX1) in complex with iron-sulfur cluster". To be published. doi:10.2210/pdb3p1m/pdb. 
  9. ^ Fukuyama K, Matsubara H, Katsube Y, Tsukihara T (1989). "Structure of [4Fe-4S] ferredoxin from Bacillus thermoproteolyticus refined at 2.3 A resolution. Structural comparisons of bacterial ferredoxins". J. Mol. Biol. 210 (2): 383–398. doi:10.1016/0022-2836(89)90338-0. PMID 2600971. 
  10. ^ Sieker LC, Meyer J, Moulis JM, Fanchon E, Duee ED, Vicat J (1994). "Refined crystal structure of the 2[4Fe-4S] ferredoxin from Clostridium acidurici at 1.84 A resolution". J. Mol. Biol. 243 (4): 683–695. doi:10.1016/0022-2836(94)90041-8. PMID 7966291. 

Further reading[edit]

  • Bruschi, M. and Guerlesquin, F. (1988). "Structure, function and evolution of bacterial ferredoxins". FEMS Microbiol. Rev. 4 (2): 155–75. PMID 3078742. 
  • Ciurli, S. and Musiani, F. (2005). "High potential iron-sulfur proteins and their role as soluble electron carriers in bacterial photosynthesis: tale of a discovery". Photosynth. Res. 85 (1): 115–131. doi:10.1007/s11120-004-6556-4. PMID 15977063. 
  • Fukuyama, K. (2004). "Structure and function of plant-type ferredoxins". Photosynth. Res. 81 (3): 289–301. doi:10.1023/B:PRES.0000036882.19322.0a. PMID 16034533. 
  • Grinberg, A.V., Hannemann, F., Schiffler, B., Müller, J., Heinemann, U. and Bernhardt, R. (2000). "Adrenodoxin: structure, stability, and electron transfer properties". Proteins 40 (4): 590–612. doi:10.1002/1097-0134(20000901)40:4<590::AID-PROT50>3.0.CO;2-P. PMID 10899784. 
  • Holden,H.M., Jacobson, B.L., Hurley, J.K., Tollin, G., Oh, B.H., Skjeldal, L., Chae, Y.K., Cheng, H., Xia, B. and Markley, J.L. (1994). "Structure-function studies of [2Fe-2S] ferredoxins". J. Bioenerg. Biomembr. 26 (1): 67–88. doi:10.1007/BF00763220. PMID 8027024. 
  • Meyer, J. (2001). "Ferredoxins of the third kind". FEBS Lett. 509 (1): 1–5. doi:10.1016/S0014-5793(01)03049-6. PMID 11734195. 

External links[edit]

  • IPR006057 - 2Fe-2S ferredoxin subdomain
  • IPR001055 - Adrenodoxin
  • IPR001450 - 4Fe-4S ferredoxin, iron-sulfur binding
  • IPR000170 - High potential iron-sulfur protein
  • PDB 1F37 - X-ray structure of thioredoxin-like ferredoxin from Aquifex aeolicus (AaFd)

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2Fe-2S iron-sulfur cluster binding domain Provide feedback

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Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001041

Ferredoxins are small, acidic, electron transfer proteins that are ubiquitous in biological redox systems. They have either 4Fe-4S, 3Fe-4S, or 2Fe-2S cluster. Among them, ferredoxin with one 2Fe-2S cluster per molecule are present in plants, animals, and bacteria, and form a distinct Ferredoxin family [PUBMED:2065785]. 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.

Several structures of the 2Fe-2S ferredoxin-type domain have been determined [PUBMED:8586613]. The domain is classified as a beta-grasp, which is characterised as having a beta-sheet comprised of four beta-strands and one alpha-helix flanking the sheet. The two Fe atoms are coordinated tetrahedrally by the two inorganic S atoms and four cysteinyl S atoms.

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Fer2 (CL0486), which has the following description:

The 2Fe-2S ferredoxin family have a general core structure consisting of beta(2)-alpha-beta(2) which abeta-grasp type fold. The domani is around one hundred amino acids with four conserved cysteine residues to which the 2Fe-2S cluster is ligated.

The clan contains the following 5 members:

DHODB_Fe-S_bind Fer2 Fer2_2 Fer2_3 Fer2_4

Alignments

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

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  Seed
(206)
Full
(17474)
Representative proteomes NCBI
(17310)
Meta
(7619)
RP15
(1464)
RP35
(3188)
RP55
(4405)
RP75
(5439)
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  Seed
(206)
Full
(17474)
Representative proteomes NCBI
(17310)
Meta
(7619)
RP15
(1464)
RP35
(3188)
RP55
(4405)
RP75
(5439)
Alignment:
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  Seed
(206)
Full
(17474)
Representative proteomes NCBI
(17310)
Meta
(7619)
RP15
(1464)
RP35
(3188)
RP55
(4405)
RP75
(5439)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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

HMM logo

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

Trees

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

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Curation and family details

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

Curation View help on the curation process

Seed source: Prosite
Previous IDs: fer2;
Type: Domain
Author: Sonnhammer ELL
Number in seed: 206
Number in full: 17474
Average length of the domain: 75.20 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 24.22 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 15.0
Trusted cut-off 20.7 15.4
Noise cut-off 20.6 14.9
Model length: 78
Family (HMM) version: 22
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Species distribution

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Interactions

There are 15 interactions for this family. More...

Fe_hyd_SSU NAD_binding_1 Fer4 Succ_DH_flav_C CO_deh_flav_C FeThRed_B Ald_Xan_dh_C FAD_binding_6 Cytochrom_C Fer2_2 FAD_binding_5 Ald_Xan_dh_C2 Sdh_cyt Fer2 FAD_binding_2

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Fer2 domain has been found. There are 266 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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