Iron also proteins

The lUBMB Commission on Nomenclature has issued a number of recommendations dealing with areas of a more biochemical nature (72), such as peptide hormones (86), conformation of polypeptide chains (87), abbreviations for nucleic acids and polynucleotides (88), iron—sulfur proteins (89), enzyme units (90), etc. The Commission has also produced rules and recommendations for naming enzymes (91,92). 

Wachtershanser has also suggested that early metabolic processes first occurred on the surface of pyrite and other related mineral materials. The iron-sulfur chemistry that prevailed on these mineral surfaces may have influenced the evolution of the iron-sulfur proteins that control and catalyze many reactions in modern pathways (including the succinate dehydrogenase and aconitase reactions of the TCA cycle). 

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. 

Contact shifts give information on the electronic structure of the iron atoms, particularly on the valence distribution and on the magnetic coupling within polymetallic systems. The magnetic coupling scheme, which is considered later, fully accounts for the variety of observed hyperfine shifts and the temperature dependence. Thus, through the analysis of the hyperfine shifts, NMR provides detailed information on the metal site(s) of iron-sulfur proteins, and, thanks to the progress in NMR spectroscopy, also the solution structure 23, 24 ). 

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 ...

Table III reports structural statistics relative to the solution structures of iron-sulfur proteins available from the Protein Data Bank (118). The lowest percentage of residue assignment occurs for oxidized Synechococcus elongatus Fd (119). The highest percentage of proton assignment is instead obtained for oxidized E. halophila HiPIP, with a value as high as 95% (120). A close figure was also obtained for the reduced protein (94%). In the latter case, such high values are obtained also thanks to the availability of labeled...

CODH/ACS is an extremely oxygen-sensitive protein that has been found in anaerobic microbes. It also is one of the three known nickel iron-sulfur proteins. Some authors would consider that there are only two, since the CODH and ACS activities are tightly linked in many organisms. However, there is strong evidence that the ACS and CODH activities are associated with different protein subunits and the reactions that the two enzymes catalyze are quite different. CODH catalyzes a redox reaction and ACS catalyzes the nonredox condensation of a methyl group, a carbonyl group, and an organic thiol (coenzyme A). 

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). 

We thank Dr Mahesh Sundararajan for helpful discussion regarding the modelling of iron containing proteins and Dr Richard Bryce for discussion regarding the modelling of carbohydrates in solution. We also thank Dr James J. P. Stewart for helpful discussion regarding the gradient-based optimisation of semi-empirical parameters. 

Although also iron-sulfur proteins, the rubredoxins do not generate H2S on acidification since in this case the thiol groups are contributed by cysteinyl residues in the polypeptide chain. The function of clostridial rubredoxin is as yet unknown in Pseudomonas sp. a similar protein catalyzes the co-hydroxylation of alkanes, a reaction requiring molecular O2. 

There is some evidence that the iron-sulfur protein, FhuF, participates in the mobilization of iron from hydroxamate siderophores in E. coli (Muller et ah, 1998 Hantke, K. unpublished observations). However, a reductase activity of FhuF has not been demonstrated. Many siderophore-iron reductases have been shown to be active in vitro and some have been purified. The characterization of these reductases has revealed them to be flavin reductases which obtain the electrons for flavin reduction from NAD(P)H, and whose main functions are in areas other than reduction of ferric iron (e.g. flavin reductase Fre, sulfite reductase). To date, no specialized siderophore-iron reductases have been identified. It has been suggested that the reduced flavins from flavin oxidoreductases are the electron donors for ferric iron reduction (Fontecave et ah, 1994). Recently it has been shown, after a fruitless search for a reducing enzyme, that reduction of Co3+ in cobalamin is achieved by reduced flavin. Also in this case it was suggested that cobalamins and corrinoids are reduced in vivo by flavins which may be generated by the flavin... 

The regulatory network of IRPs appears also to connect the synthesis of protoporphyrin IX in erythroid cells, and of certain mitochondrial iron-sulfur proteins to iron bioavailability (reviewed in Hentze and Kuhn, 1996). mRNAs encoding erythroid... 

---