Home ScanProsite ProRule Documents Downloads Links Funding
	PROSITE documentation PDOC00176

4Fe-4S ferredoxin-type iron-sulfur binding domain signature and profile

Ferredoxins [1] are a group of iron-sulfur proteins which mediate electron transfer in a wide variety of metabolic reactions. Ferredoxins can be divided into several subgroups depending upon the physiological nature of the iron-sulfur cluster(s). One of these subgroups are the 4Fe-4S ferredoxins, which are found in bacteria and which are thus often referred as 'bacterial-type' ferredoxins. The structure of these proteins [2] consists of the duplication of a domain of twenty six amino acid residues; each of these domains contains four cysteine residues that bind to a 4Fe-4S center.

Several structures of the 4Fe-4S ferredoxin domain have been determined (see for example <PDB:1FDN>) [3]. The clusters consist of two interleaved 4Fe- and 4S-tetrahedra forming a cubane-like structure, in such a way that the four iron occupy the eight corners of a distorted cube. Each 4Fe-4S is attached to the polypeptide chain by four covalent Fe-S bonds involving cysteine residues.

A number of proteins have been found [4] that include one or more 4Fe-4S binding domains similar to those of bacterial-type ferredoxins. These proteins are listed below:

• The iron-sulfur proteins of the succinate dehydrogenase and the fumarate reductase complexes (EC 1.3.99.1). These enzyme complexes, which are components of the tricarboxylic acid cycle, each contain three subunits: a flavoprotein, an iron-sulfur protein, and a b-type cytochrome. The iron- sulfur proteins contain three different iron-sulfur centers: a 2Fe-2S, a 3Fe-4S and a 4Fe-4S.
• Escherichia coli anaerobic glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) This enzyme is composed of three subunits: A, B, and C. The C subunit seems to be an iron-sulfur protein with two ferredoxin-like domains in the N- terminal part of the protein.
• Escherichia coli anaerobic dimethyl sulfoxide reductase. The B subunit of this enzyme (gene dmsB) is an iron-sulfur protein with four 4Fe-4S ferredoxin-like domains.
• Escherichia coli formate hydrogenlyase. Two of the subunits of this oligomeric complex (genes hycB and hycF) seem to be iron-sulfur proteins that each contain two 4Fe-4S ferredoxin-like domains.
• Methanobacterium formicicum formate dehydrogenase (EC 1.2.1.2). This enzyme is used by the archaebacteria to grow on formate. The β chain of this dimeric enzyme probably binds two 4Fe-4S centers.
• Escherichia coli formate dehydrogenases N and O (EC 1.2.1.2). The β chain of these two enzymes (genes fdnH and fdoH) are iron-sulfur proteins with four 4Fe-4S ferredoxin-like domains.
• Desulfovibrio periplasmic [Fe] hydrogenase (EC 1.18.99.1). The large chain of this dimeric enzyme binds three 4Fe-4S centers, two of which are located in the ferredoxin-like N-terminal region of the protein.
• Methanobacterium thermoautrophicum methyl viologen-reducing hydrogenase subunit mvhB, which contains six tandemly repeated ferredoxin-like domains and which probably binds twelve 4Fe-4S centers.
• Salmonella typhimurium anaerobic sulfite reductase (EC 1.8.1.-) [5]. Two of the subunits of this enzyme (genes asrA and asrC) seem to both bind two 4Fe-4S centers.
• A Ferredoxin-like protein (gene fixX) from the nitrogen-fixation genes locus of various Rhizobium species, and one from the Nif-region of Azotobacter species.
• The 9 Kd polypeptide of chloroplast photosystem I [6] (gene psaC). This protein contains two low potential 4Fe-4S centers, referred as the A and B centers.
• The chloroplast frxB protein which is predicted to carry two 4Fe-4S centers.
• An ferredoxin from a primitive eukaryote, the enteric amoeba Entamobea histolytica.
• Escherichia coli hypothetical protein yjjW, a protein with a N-terminal region belonging to the radical activating enzymes family (see <PDOC00834>) and two potential 4Fe-4S centers.

The pattern of cysteine residues in the iron-sulfur region is sufficient to detect this class of 4Fe-4S binding proteins. The profile we developed covers the whole domain.

Note:

In some bacterial ferredoxins, one of the two duplicated domains has lost one or more of the four conserved cysteines. The consequence of such variations is that these domains have either lost their iron-sulfur binding property or bind to a 3Fe-4S center instead of a 4Fe-4S center.

Note:

The last residue of this pattern in most proteins belonging to this group, is a Pro; the only exceptions are the Rhizobium ferredoxin-like proteins which have Gly, and two Desulfovibrio ferredoxins which have Glu. It must also be noted that the three non 4Fe-4S-binding proteins which are picked-up by the pattern have Gly in this position of the pattern.

Last update:

April 2008 / Text revised; profile added.

PROSITE methods (with tools and information) covered by this documentation:

4FE4S_FER_2, PS51379; 4Fe-4S ferredoxin-type iron-sulfur binding domain profile  (MATRIX)

• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 1463
  • detected by PS51379: 1424 (true positives)
  • undetected by PS51379: 39 (37 false negatives and 2 'partials')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS51379:
  8 false positives and 4 unknowns.
• Domain architecture view of Swiss-Prot proteins matching PS51379
  
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS51379
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS51379
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS51379
• View ligand binding statistics of PS51379
• Matching PDB structures: 1A6L 1AXQ 1B0P 1B0T ... [ALL]

4FE4S_FER_1, PS00198; 4Fe-4S ferredoxin-type iron-sulfur binding region signature  (PATTERN)

• Consensus pattern:
  C-x-{P}-C-x(2)-C-{CP}-x(2)-C-[PEG]
  The 4 C's are 4Fe-4S ligands
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 1441
  • detected by PS00198: 1396 (true positives)
  • undetected by PS00198: 45 (41 false negatives and 4 'partials')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00198:
  17 false positives and 4 unknowns.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00198
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00198
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00198
• View ligand binding statistics of PS00198
• Matching PDB structures: 1A6L 1AXQ 1B0P 1B0T ... [ALL]

1	Authors	Meyer J.
	Title	The evolution of ferredoxins.
	Source	Trends Ecol. Evol. 3:222-226(1988).

2	Authors	Otaka E., Ooi T.
	Title	Examination of protein sequence homologies: IV. Twenty-seven bacterial ferredoxins.
	Source	J. Mol. Evol. 26:257-267(1987).
	PubMed ID	3129571

3	Authors	Duee E.D., Fanchon E., Vicat J., Sieker L.C., Meyer J., Moulis J.M.
	Title	Refined crystal structure of the 2[4Fe-4S] ferredoxin from Clostridium acidurici at 1.84 A resolution.
	Source	J. Mol. Biol. 243:683-695(1994).
	PubMed ID	7966291

4	Authors	Beinert H.
	Title	Recent developments in the field of iron-sulfur proteins.
	Source	FASEB J. 4:2483-2491(1990).
	PubMed ID	2185975

5	Authors	Huang C.J., Barrett E.L.
	Title	Sequence analysis and expression of the Salmonella typhimurium asr operon encoding production of hydrogen sulfide from sulfite.
	Source	J. Bacteriol. 173:1544-1553(1991).
	PubMed ID	1704886

6	Authors	Knaff D.B.
	Title	The photosystem I reaction centre.
	Source	Trends Biochem. Sci. 13:460-461(1988).

PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to

Prosite License or see: prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)