Ferredoxins  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  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>) . 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  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 126.96.36.199). 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 188.8.131.52)
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
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 184.108.40.206). 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 220.127.116.11). 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 18.104.22.168). 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.-) . Two of
the subunits of this enzyme (genes asrA and asrC) seem to both bind two
A Ferredoxin-like protein (gene fixX) from the nitrogen-fixation genes
locus of various Rhizobium species, and one from the Nif-region of
The 9 Kd polypeptide of chloroplast photosystem I  (gene psaC). This
protein contains two low potential 4Fe-4S centers, referred as the A and B
The chloroplast frxB protein which is predicted to carry two 4Fe-4S centers.
An ferredoxin from a primitive eukaryote, the enteric amoeba Entamobea
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.
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.
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.
April 2008 / Text revised; profile added.
PROSITE methods (with tools and information) covered by this documentation:
The evolution of ferredoxins.
Trends Ecol. Evol. 3:222-226(1988).
Otaka E., Ooi T.
Examination of protein sequence homologies: IV. Twenty-seven bacterial ferredoxins.
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
or see: prosite_license.html.