In almost all Fe–S proteins, the Fe centers are tetrahedral and the terminal ligands are thiolato sulfur centers from cysteinyl residues. The sulfide groups are either two- or three-coordinated. Three distinct kinds of Fe–S clusters with these features are most common.
Structure-function principles Iron–sulfur proteins are involved in various biological electron transport processes, such as photosynthesis and cellular respiration, which require rapid electron transfer to sustain the energy or biochemical needs of the organism. To serve their various biological roles, iron-sulfur proteins effect rapid electron transfers and span the whole range of physiological redox potentials from -600 mV to +460 mV. Fe3+-SR bonds have unusually high covalency which is expected. When comparing the covalency of Fe3+ with the covalency of Fe2+, Fe3+ has almost double the covalency of Fe2+ (20% to 38.4%). Fe3+ is also much more stabilized than Fe2+. Hard ions like Fe3+ normally have low covalency because of the energy mismatch of the metal
lowest unoccupied molecular orbital with the ligand
highest occupied molecular orbital. External water molecules positioned close to the iron-sulfur active site reduces covalency; this can be shown by
lyophilization experiments where water is removed from the protein. This reduction is because external water
hydrogen bonds with cysteine S, decreasing the latter's lone pair electron donation to the Fe3+/2+ by pulling away S electrons. This high covalency lowers the inner sphere reorganization energy
4Fe–4S clusters A common motif features a four iron ions and four sulfide ions placed at the vertices of a
cubane-type cluster. The Fe centers are typically further coordinated by cysteinyl ligands. The [Fe4S4] electron-transfer proteins ([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: In HiPIP, the cluster shuttles between [2Fe3+, 2Fe2+] (Fe4S42+) and [3Fe3+, Fe2+] (Fe4S43+). The potentials for this redox couple range from 0.4 to 0.1 V. In the bacterial ferredoxins, the pair of oxidation states are [Fe3+, 3Fe2+] (Fe4S4+) and [2Fe3+, 2Fe2+] (Fe4S42+). The potentials for this redox couple range from −0.3 to −0.7 V. The two families of 4Fe–4S clusters share the Fe4S42+ oxidation state. The difference in the redox couples is attributed to the degree of hydrogen bonding, which strongly modifies the basicity of the cysteinyl thiolate ligands. A further redox couple, which is still more reducing than the bacterial ferredoxins is implicated in the
nitrogenase. Some 4Fe–4S clusters bind substrates and are thus classified as enzyme cofactors. In
aconitase, the Fe–S cluster binds
aconitate at the one Fe centre that lacks a thiolate ligand. The cluster does not undergo redox, but serves as a
Lewis acid catalyst to convert citrate to
isocitrate. In
radical SAM enzymes, the cluster binds and reduces
S-adenosylmethionine to generate a radical, which is involved in many biosyntheses. The second cubane shown here with mixed valence pairs (2 Fe3+ and 2 Fe2+), has a greater stability from covalent communication and strong covalent delocalization of the “extra” electron from the reduced Fe2+ that results in full ferromagnetic coupling.
3Fe–4S clusters Proteins are also known to contain [Fe3S4] centres, which feature one iron less than the more common [Fe4S4] cores. Three sulfide ions bridge two iron ions each, while the fourth sulfide bridges three iron ions. Their formal oxidation states may vary from [Fe3S4]+ (all-Fe3+ form) to [Fe3S4]2− (all-Fe2+ form). In a number of iron–sulfur proteins, the [Fe4S4] cluster can be reversibly converted by oxidation and loss of one iron ion to a [Fe3S4] cluster. E.g., the inactive form of
aconitase possesses an [Fe3S4] and is activated by addition of Fe2+ and reductant.
Other Fe–S clusters Examples include the active sites of a number of enzymes: • cluster in
nitrogenase. The cluster is linked to the protein by the amino acid residues
cysteine and
histidine.
Nitrogenase include two P-clusters ([8Fe-7S]) and two
FeMocos ([7Fe-9S-C-Mo-
R homocitrate]). •
Carbon monoxide dehydrogenase and
acetyl coenzyme-A synthase each features an Fe-N-iS4 clusters. • [FeFe]-
hydrogenase features an "H-cluster", consisting of a Fe4S4 bridge to Fe2 via a cystine. The Fe2 half features unique ligands: 3 CO, 2 CN−, and an azadithiolate HN(CH2S−)2. • A special 6 cysteine-coordinated [Fe4S3] cluster was found in oxygen-tolerant membrane-bound [NiFe] hydrogenases. • The "double cubane cluster" [Fe8S9], found in some nitrogenase-related ATPases, consists of two [Fe4S4] bridged by a cysteine. The functions of such proteins remain unclear. ==Biosynthesis==