Iron-sulfur protein/cluster

Berg JM, Hohn RH. 1982. Structures and reactions of iron-sulfur protein clusters and their synthetic analogs. In Spiro TG, editor. Iron-sulfur proteins. New York Wiley-Interscience. p 1-66. 

The [4Fe-4S] cluster in AOR and FOR is paramagnetic in its reduced form and displays characteristic EPR resonances, although the spin relaxation rate is very fast and the spectra are observed only at very low temperatures (see Iron-Sulfur Proteins). Hence, at 4K, the EPR spectrum of AOR is dominated by resonances from its reduced Fe-S cluster. However, this gives rise to a rhombic signal from a S = 3/2 ground state, while reduced 4Fe-clusters typically have an S = 1/2 ground state. In fact, while mixed spin, S = 3/2 and S = 1/2 reduced [4Fe-4S] clusters are sometimes observed in some iron-sulfur proteins (see Iron-Sulfur Proteins), clusters that have exclusively S = 3 /2 ground states are so far unique to AOR. Indeed, the reduced 4Fe-cluster of FOR has a mixed spin state with S = 3/2 (80%) and S = 1/2 (20%) components. The factors that determine the spin state of a [4Fe-4S] center have yet to be elucidated. 

In 1964, Rieske and co-workers reported the observation of an EPR signal around g = 1.90 in the cytochrome bci complex (1). They succeeded in the isolation of the iron sulfur protein that gave rise to the EPR signal and showed that it contained a [2Fe-2S] cluster. Over the... 

Although the redox potential of Rieske-type clusters is approximately 400 mV lower than that of Rieske clusters, it is 300 mV more positive than the redox potential of plant-type ferredoxins (approximately -400 mV). Multiple factors have been considered to be essential for the redox potential of iron sulfur proteins ... 

Since their discovery, Rieske proteins have been the object of numerous studies aimed at gaining insight into the molecular basis of their unique properties. These studies not only have shed light on Rieske and Rieske-type clusters, but also have contributed to the understanding of iron sulfur proteins in general. 

For all known cases of iron-sulfur proteins, J > 0, meaning that the system is antiferromagnetically coupled through the Fe-S-Fe moiety. Equation (4) produces a series of levels, each characterized by a total spin S, with an associated energy, which are populated according to the Boltzmann distribution. Note that for each S level there is in principle an electron relaxation time. For most purposes it is convenient to refer to an effective relaxation time for the whole cluster. 

Table I reports the observed NMR linewidths for the H/3 protons of the coordinating cysteines in a series of iron-sulfur proteins with increasing nuclearity of the cluster, and in different oxidation states. We have attempted to rationalize the linewidths on the basis of the equations describing the Solomon and Curie contributions to the nuclear transverse relaxation rate [Eqs. (1) and (2)]. When dealing with polymetallic systems, the S value of the ground state has been used in the equations. When the ground state had S = 0, reference was made to the S of the first excited state and the results were scaled for the partial population of the state. In addition, in polymetallic systems it is also important to account for the fact that the orbitals of each iron atom contribute differently to the populated levels. For each level, the enhancement of nuclear relaxation induced by each iron is proportional to the square of the contribution of its orbitals (54). In practice, one has to calculate the following coefficient for each iron atom ...

As mentioned in the Introduction, in iron—sulfur proteins, the hyperfine shifts of the nuclei of the coordinating cysteines are essentially contact in origin (21, 22). In the case of [Fe4S4l (17) and [FegS4] (112) cluster, it has been shown that the hyperfine shift of the cysteinyl H/3 and Ca nuclei can be related to the value of the Fe-Sy-C/S-H/S/Ca dihedral angle (6) through a Karplus-type relationship of the form... 

This review concerns proteins that contain both nickel and iron. Below are listed the three known proteins of this class and the reactions that they catalyze. The active sites of all of these consist of het-erometallic nickel-iron-sulfur (NiFeS) clusters. The terms used will he explained later in the text. 

Fig. 11. Active sites and reactions of the bifunctional CODH/ACS. For synthesis of acetyl-CoA, two electrons are transferred from external electron donors to Cluster B of the CODH subunit. Electrons are relayed to Cluster C which reduces CO2 to CO. The CO is proposed to be channeled to Cluster A of the ACS subunit to form a metal-CO adduct that combines with the methyl group of the CFeSP and CoA to form acetyl-CoA. For utilization of acetyl-CoA, these reactions are reversed. The abbreviations are CODH, CO dehydrogenase ACS, acetyl-CoA synthase CFeSP, the corrinoid iron-sulfur protein CoA, Coenzyme A.

During the 1960s, research on proteins containing iron—sulfur clusters was closely related to the field of photosynthesis. Whereas the first ferredoxin, a 2[4Fe-4S] protein, was obtained in 1962 from the nonphotosynthetic bacterium Clostridium pasteurianum (1), in the same year, a plant-type [2Fe-2S] ferredoxin was isolated from spinach chloroplasts (2). Despite the fact that members of this latter class of protein have been reported for eubacteria and even archaebacteria (for a review, see Ref. (3)), the name plant-type ferredoxin is often used to denote this family of iron—sulfur proteins. The two decades... 

It has always been assumed that these simple proteins act as electron-transfer proteins. This is also a fair conclusion if we take in account that different proteins were isolated in which the Fe(RS)4 center is in association with other non-heme, non-iron-sulfur centers. In these proteins the Fe(RS)4 center may serve as electron donor/ac-ceptor to the catalytic site, as in other iron-sulfur proteins where [2Fe-2S], [3Fe-4S], and [4Fe-4S] clusters are proposed to be involved in the intramolecular electron transfer pathway (see the following examples). 

In particular, the study of SRB ferredoxins enables us to survey the different properties of simple iron-sulfur proteins, including electron transfer, flexibility in coordination chemistry, and ability to undergo cluster interconversions. Most of the observations can be extrapolated to more complex situations. 

A preliminaiy characterization of a new iron—sulfur protein isolated from Desulfovibrio vulgaris Hildenborough was reported in 1989 124). The protein contained approximately 6 iron and 6 inorganic sulfur atoms per molecule. The FPR spectrum of the dithionite reduced protein exhibited an S = signal similar to what was found for synthetic compounds with a [6Fe-6S] core (prismane core). No other FPR signals were reported at this time, and based on the observed similarity it was suggested that this peculiar iron-sulfur protein contained a [6Fe-6S] cluster. Because it had no known function, the pro-... 

Although iron-sulfur proteins are found in various cellular localizations in eukaryotic cells, mitochondria are the major site of Fe-S cluster biosynthesis (Lill et ah, 1999). Deletions in nuclear genes involved in mitochondrial iron-sulfur cluster formation lead to massive accumulation of iron in mitochondria (Chapter 7). For example, deletion of ATM1, a mitochondrial ATPase, which seems to be responsible for the export of Fe-S clusters, leads to respiratory incompetence, excessive iron accumulation and leucine auxotrophy (Kispal et ah, 1999). In Ayfhl cells there is only partial loss of mitochondrial Fe-S enzymes and the cells are not leucine auxotrophs. 

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