Iron-sulfur clusters HIPIP

Fig. 1. Iron-sulfur clusters basic building blocks. In most cases the iron is tetrahe-drally coordinated by sulfur from cysteinyl residues (and labile sulfur). Variability on coordination is allowed (see text). A, Rubredoxin type FeS4 (simplest cluster, no labile sulfur) B, plant-type ferredoxin [2Fe-2S] C, bacterial ferredoxin [3Fe-4S] D, bacterial ferredoxin and HiPIP [4Fe-4S] E, novel cluster [4Fe-2S, 20] ( hybrid cluster ).

A brief historical note on the structure of the iron-sulfur clusters in ferredoxins is relevant. After the first analytical results revealed the presence of (nearly) equimolar iron and acid-labile sulfur, it was clear that the metal center in ferredoxins did not resemble any previously characterized cofactor type. The early proposals for the Fe S center structure were based on a linear chain of iron atoms coordinated by bridging cysteines and inorganic sulfur (Blomstrom et al., 1964 Rabino-witz, 1971). While the later crystallographic analyses of HiPIP, PaFd, and model compounds (Herskovitz et al., 1972) demonstrated the cubane-type structure of the 4Fe 4S cluster, the original proposals have turned out to be somewhat prophetic. Linear chains of sulfide-linked irons are observed in 2Fe 2S ferredoxins and in the high-pH form of aconitase. Cysteines linked to several metal atoms are present in metallothionein. The chemistry of iron-sulfur clusters is rich and varied, and undoubtedly many other surprises await in the future. 

Another group of related electron carriers, the high-potential iron proteins (HIPIP) contain four labile sulfur and four iron atoms per peptide chain 261-266 X-ray studies showed that the 86-residue polypeptide chain of the HIPIP of Chromatium is wrapped around a single iron-sulfur cluster which contains the side chains of four cysteine residues plus the four iron and four sulfur atoms (Fig. 16-15D)261 This kind of cluster is referred to as [4Fe-4S], or as Fe4S4. Each cysteine sulfur is attached to one atom of Fe, with the four iron atoms forming an irregular tetrahedron with an Fe-Fe... 

Some detailed comparisons of the protein environments around the HiPIP and Fd clusters have been made.769,770 It is noteworthy that the HiPIP cluster is more deeply buried (about 4.5 A) than is the case for the clusters in the other iron-sulfur proteins. All iron-sulfur proteins for which structural data are available, with the exception of the three-iron protein from Azotobacter vinelandii, have hydrogen bonding between the cysteine sulfur in the iron-sulfur cluster and the backbone peptide link. It appears that there is an approximate correlation between the number of NH S hydrogen bonds in the environment of a cluster and its redox potential. In HiPIP, these hydrogen bonds become more linear and shorten on reduction of the cluster. It is possible, therefore, that the oxidation states of the cluster may be controlled by the geometries of the hydrogen bonds.770... 

E. coli uses nitrate as a terminal electron acceptor through a respiratory, dissimilatory nitrate reductase whose synthesis is induced when nitrate is provided, and which is repressed by oxygen. Nitrate reductase is discussed with other molybdoenzymes in Section 62.1.9, and catalyzes the reduction of nitrate to nitrite. The enzyme is isolated from the cytoplasmic membrane of E. coli, and contains three subunits (a, j8 and y) although the y-subunit may be absent in some preparations. The -y-subunit is a b-type cytochrome, and the a-subunit is reported to be the catalytic subunit. The enzyme contains a number of iron-sulfur clusters, including a HiPIP and at least two ferredoxins.1054,1437... 

This cluster formally contains three iron(III) and one iron(E). It is present in a class of proteins called high potential iron-sulfur proteins (HiPIP). It has also been prepared through oxidation of [(RS)4Fe4S4]2 model compounds [57]. Both in the model compound at low temperatures and in proteins there is electron delocalization on one mixed valence pair [58-62]. Therefore, the polymetallic center is constituted by two iron ions at the oxidation state +2.5 and two iron ions at the oxidation state +3. Hamiltonian (6.20), or a more complicated one [40, 41,43], can be used to describe the electronic structure. Indeed, a delocalization operator is sometimes needed in the Hamiltonian [40,41,43]. Consistently with magnetic Mossbauer data the S M subspin involving the mixed valence pair is 9/2, whereas the S n subspin involving the iron(IH) ions is 4. Mossbauer and EPR data do not exclude % and 3, respectively, for the two pairs [57] in any case, the... 

The most thoroughly investigated high-potential iron-sulfur protein (HiPIP) is that isolated for Chromatium vinosum (a purple photosynthetic bacterium). The reduction potential of the iron-sulfur cluster is 350 mV, and the overall charge on the protein is -3 the Fc4S4 cluster is buried within the 9500-Da protein, ligated to cysteines at positions 43,45,63, and 77 (Fig. 12) (1, 18). Several studies have been made of the oxidation and reduction of HiPIP by inorganic complexes (40, 62, 131, 153). 

High potential iron-sulfur protein (HiPIP) is a special type of Fd which has been isolated from some photosynthetic bacteria and detected by ESR spectroscopy in other bacteria. HiPIP also contains a single 4Fe-4S cluster, but it differs from the other Fd in having a positive standard potential of about-h 350 mV (most Fd have standard potentials in the range of the hydrogen electrode, about -420 mV). Furthermore, the HiPIP from Chromatium is paramagnetic in the oxidized state. 

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