2Fe-2S ferredoxin-type iron-sulfur binding domain signature and profile

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 2Fe-Ferredoxin family [1,2]. 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 domain have been determined (see for example <PDB:4FXC>) [3]. The domain is classified as a β-grasp which is characterized as having a β-sheet comprised of four β-strands and one α-helix flanking the sheet [4]. The two Fe atoms are coordinated tetrahedrally by the two inorganic S atoms and four cysteinyl S atoms.

Some proteins that contains a 2Fe-2S ferredoxin-type domain are listed below:

• Ferredoxin from photosynthetic organisms; namely plants and algae where it is located in the chloroplast or cyanelle; and cyanobacteria.
• Ferredoxin from archaebacteria of the Halobacterium genus.
• Ferredoxin IV (gene pftA) and V (gene fdxD) from Rhodobacter capsulatus.
• Ferredoxin in the toluene degradation operon (gene xylT) and naphthalene degradation operon (gene nahT) of Pseudomonas putida.
• Hypothetical Escherichia coli protein yfaE.
• The N-terminal domain of the bifunctional ferredoxin/ferredoxin reductase electron transfer component of the benzoate 1,2-dioxygenase complex (gene benC) from Acinetobacter calcoaceticus, the toluene 4-monooxygenase complex (gene tmoF), the toluate 1,2-dioxygenase system (gene xylZ), and the xylene monooxygenase system (gene xylA) from Pseudomonas.
• The N-terminal domain of phenol hydroxylase protein p5 (gene dmpP) from Pseudomonas Putida.
• The N-terminal domain of methane monooxygenase component C (gene mmoC) from Methylococcus capsulatus .
• The C-terminal domain of the vanillate degradation pathway protein vanB in a Pseudomonas species.
• The N-terminal domain of bacterial fumarate reductase iron-sulfur protein (gene frdB).
• The N-terminal domain of CDP-6-deoxy-3,4-glucoseen reductase (gene ascD) from Yersinia pseudotuberculosis.
• The central domain of eukaryotic succinate dehydrogenase (ubiquinone) iron- sulfur protein.
• The N-terminal domain of eukaryotic xanthine dehydrogenase.
• The N-terminal domain of eukaryotic aldehyde oxidase.

Three of the four conserved cysteines are clustered together in the same region of the protein. Our signature pattern spans that iron-sulfur binding region. We also developed a profile that covers the whole domain.