Enzymes iron-sulfur 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). 

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). 

Formate dehydrogenases are a diverse group of enzymes found in both prokaryotes and eukaryotes, capable of converting formate to CO2. Formate dehydrogenases from anaerobic microorganisms are, in most cases, Mo- or W- containing iron-sulfur proteins and additionally flavin or hemes. Selenium cysteine is a Mo- ligand. 

H)2-D3 is a weak agonist and must be modified by hydroxylation at position Cj for full biologic activity. This is accomplished in mitochondria of the renal proximal convoluted tubule by a three-component monooxygenase reaction that requires NADPFl, Mg, molecular oxygen, and at least three enzymes (1) a flavoprotein, renal ferredoxin reductase (2) an iron sulfur protein, renal ferredoxin and (3) cytochrome P450. This system produces l,25(OH)2-D3, which is the most potent namrally occurring metabolite of vitamin D. 

The many redox reactions that take place within a cell make use of metalloproteins with a wide range of electron transfer potentials. To name just a few of their functions, these proteins play key roles in respiration, photosynthesis, and nitrogen fixation. Some of them simply shuttle electrons to or from enzymes that require electron transfer as part of their catalytic activity. In many other cases, a complex enzyme may incorporate its own electron transfer centers. There are three general categories of transition metal redox centers cytochromes, blue copper proteins, and iron-sulfur proteins. 

The anaerobic degradation of some hydroxybenzoates and phenols involves reductive removal of the phenolic hydroxyl group. The enzyme that dehydroxylates 4-hydroxybenzoyl-CoA in Thauera aromatica is a molybdenum-flavin-iron-sulfur protein (Breese and Fuchs 1998), and is similar to the enzyme from the nonsulfur phototroph Rhodopseudomonas palustris that carries out the same reaction (Gibson et al. 1997). 

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... 

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. 

The reaction-center proteins for Photosystems I and II are labeled I and II, respectively. Key Z, the watersplitting enzyme which contains Mn P680 and Qu the primary donor and acceptor species in the reaction-center protein of Photosystem II Qi and Qt, probably plastoquinone molecules PQ, 6-8 plastoquinone molecules that mediate electron and proton transfer across the membrane from outside to inside Fe-S (an iron-sulfur protein), cytochrome f, and PC (plastocyanin), electron carrier proteins between Photosystems II and I P700 and Au the primary donor and acceptor species of the Photosystem I reaction-center protein At, Fe-S a and FeSB, membrane-bound secondary acceptors which are probably Fe-S centers Fd, soluble ferredoxin Fe-S protein and fp, is the flavoprotein that functions as the enzyme that carries out the reduction of NADP+ to NADPH. 

Iron-sulfur proteins are a group of enzymes and other electron carriers that contain clusters of iron and sulfide linked directly to amino-acyl side chains, usually cysteines. They are widely distributed in nature. Soon after their discovery. Hall et al. (1971) proposed that they could be used to follow the course of evolution. Studies of genome sequences have revealed that iron-sulfur cluster binding motifs are among the most commonly recognized sequences. 

Within organisms, organic sulfur is present predominantly as the amino acids cysteine and methionine, and the algal and bacterial osmolyte, dimethylsulfoniopropionate (DMSP). The latter also serves as an antioxidant and cryoprotectant. Small amounts of organosulfur are also present in some polysaccharides, lipids, vitamins, enzymes, and in the iron-sulfur protein ferrodoxin. Cell lysis and microbial degradation releases... 

In this text, iron-sulfur clusters are discussed because they appear in proteins and enzymes (1) cytochrome b(6)f, Rieske [2Fe-2S] cluster (Section 7.5 and Figure 7.26) (2) cytochrome bci, Rieske [2Fe-2S] cluster (Section 7.6 and Figure 7.30) and (3) aconitase, [4Fe-4S] cluster (Section 7.9.2.1, and Figure 7.50). The iron-sulfur protein (ISP) component of the cytochrome b(6)f and cytochrome bci complexes, now called the Rieske ISP, was first discovered and isolated by John S. Rieske and co-workers in 1964 (in the cytochrome bci complex). More information about the RISP is found in Section 7.5.1. Section 7.9.2 briefly discusses other proteins with iron-sulfur clusters—rubredoxins, ferrodoxins, and the enzyme nitrogenase. The nitrogenase enzyme was the subject of Chapter 6 in the hrst edition of this text— see especially the first edition s Section 6.3 for a discussion of iron-sulfur clusters. In this second edition, information on iron-sulfur clusters in nitrogenase is found in Section 3.6.4. See Table 3.2 and the descriptive examples discussed in Section 3.6.4. 

The preceding sections of Chapter 7 have discussed iron-containing proteins and enzymes having a porphyrin ring system. Section 7.9 presents a short introduction to the many non-heme iron-containing proteins and enzymes. Two of these are iron-sulfur proteins (Section 7.9.2) and iron-oxo proteins (Section 7.9.3). 

One large class of non-heme iron-containing biomolecules involves proteins and enzymes containing iron-sulfur clusters. Iron-sulfur clusters are described in Sections 1.7 (Bioorganometallic Chemistry) and 1.8 (Electron Transfer) as well as in Section 3.6 (Mossbauer Spectroscopy). See especially Table 3.2 and the descriptive examples discussed in Section 3.6.4. Iron-sulfur proteins include rubredoxins, ferrodoxins, and the enzymes aconitase and nitrogenase. The nitrogenase enzyme was the subject of Chapter 6 in the hrst edition of this text—see especially Section 6.3 for a discussion of iron-sulfur clusters. In this... 

Iron-sulfur clusters (7) occur as prosthetic groups in oxidoreductases, but they are also found in lyases—e.g., aconitase (see p. 136) and other enzymes. Iron-sulfur clusters consist of 2-4 iron ions that are coordinated with cysteine residues of the protein (-SR) and with anorganic sulfide ions (S). Structures of this type are only stable in the interior of proteins. Depending on the number of iron and sulfide ions, distinctions are made between [Fe2S2], [Fe3S4], and [Fe4S4] clusters. These structures are particularly numerous in the respiratory chain (see p. 140), and they are found in all complexes except complex IV. 

This enzyme [EC 1.18.99.1], also known as hydrogenly-ase, catalyzes the reaction of H2 with two oxidized ferre-doxin to produce two H+ and two reduced ferredoxin. This enzyme is an iron-sulfur protein and requires nickel ions. It can use molecular hydrogen to reduce a variety of substances. See also Hydrogen Dehydrogenase Cytochrome C3 Hydrogenase... 

Adrenodoxin. Adrenodoxin is the only iron-sulfur protein which has been isolated from mammals. This protein from mitochondria of bovine adrenal cortex was purified almost simultaneously by Kimura and Suzuki (32) and Omura et al. (33). It has a molecular weight of 12,638 (34) and the oxidized form of the protein shows maximal absorbances at 415 and 453 nm. Adrenodoxin acts as an electron carrier protein in the enzyme system required for steroid hydroxylation in adrenal mitochondria. In this system, electron transfer is involved with three proteins cytochrome P. gQ, adrenodoxin and a flavoprotein. Reduced NADP gives an electron to Tne flavoprotein which passes the electron to adrenodoxin. Finally, reduced adrenodoxin transfers the electron to cytochrome Pas shown in Fig. 3. The mechanism of cytochrome P cq interaction with steroid, oxygen and adrenodoxin in mixed-function oxidase of adrenal cortex mitochondria has been reviewed by Estabrook et al. (35). 

Putidaredoxin. Cushman et al. (36) isolated a low molecular iron-sulfur protein from camphor-grown Pseudomonas putida. This protein, putidaredoxin, is similar to the plant type ferredoxins with two irons attached to two acid-labile sulfur atoms (37). It has a molecular weight of 12,000 and shows absorption maxima at 327, 425 and 455 nm. Putidaredoxin functions as an electron transfer component of a methylene hydroxylase system involved in camphor hydroxylation by P. putida. This enzyme system consists of putidaredoxin, flavoprotein and cytochrome P.cQ (38). The electron transport from flavoprotein to cytochrome P.cq is Smilar to that of the mammalian mixed-function oxidase, but requires NADH as a primary electron donor as shown in Fig. 4. In this bacterial mixed-function oxidase system, reduced putidaredoxin donates an electron to substrate-bound cytochrome P. g, and the reduced cytochrome P. g binds to molecular oxygen. One oxygen atom is then used for substrate oxidation, and the other one is reduced to water (39, 40). 

Megaredoxin. Another example of a bacterial mixed-function oxidase was found in the steroid 15 6-hydroxylase system of Bacillus megaterium (41). This enzyme system consists of three proteins FMN-containing flavoprotein (megaredoxin reductase), iron-sulfur protein... 

---