Dehydrogenases Iron-sulfur clusters

Iron Sulfur Compounds. Many molecular compounds (18—20) are known in which iron is tetrahedraHy coordinated by a combination of thiolate and sulfide donors. Of the 10 or more stmcturaHy characterized classes of Fe—S compounds, the four shown in Figure 1 are known to occur in proteins. The mononuclear iron site REPLACE occurs in the one-iron bacterial electron-transfer protein mbredoxin. The [2Fe—2S] (10) and [4Fe—4S] (12) cubane stmctures are found in the 2-, 4-, and 8-iron ferredoxins, which are also electron-transfer proteins. The [3Fe—4S] voided cubane stmcture (11) has been found in some ferredoxins and in the inactive form of aconitase, the enzyme which catalyzes the stereospecific hydration—rehydration of citrate to isocitrate in the Krebs cycle. In addition, enzymes are known that contain either other types of iron sulfur clusters or iron sulfur clusters that include other metals. Examples include nitrogenase, which reduces N2 to NH at a MoFe Sg homocitrate cluster carbon monoxide dehydrogenase, which assembles acetyl-coenzyme A (acetyl-CoA) at a FeNiS site and hydrogenases, which catalyze the reversible reduction of protons to hydrogen gas. 

Hagen, W.R., Vanoni, M.A., Rosenbaum, K., and Schnackerz, K.D. 2000. On the iron-sulfur clusters in the complex redox enzyme dihydropyrimidine dehydrogenase. European Journal of Biochemistry 267 3640-3646. 

Zirngibl, C., van Dongen, W., Schworer, B., von Biinau, R., Richter, M., Klein, A., Thauer, R. K. (1992) H2-forming methylenetetrahydromethanopterin dehydrogenase, a novel type of hydrogenase with iron-sulfur clusters in methanogenic archaea. Eur. J. Biochem. 208, 511-20. 

Salerno, J. C., Ohnishi, T., Lim, J., and King, T. E. (1976). Tetranuclear and binuclear iron-sulfur clusters in succinate dehydrogenase A method of iron quantitation by formation of paramagnetic complexes. Biochem. Biophys. Res. Commun. 73, 833-839. 

Figure 15-9 Stereoscopic view of the large domain (residues 1-383) of tri-methylamine dehydrogenase from a methylotrophic bacterium. The helices and 3 strands of the (aP)8 barrel are drawn in heavy lines as are the FMN (center) and the Fe4S4 iron-sulfur cluster at the lower right edge. The a/P loop to which it is bound is drawn with dashed lines. The 733-residue protein also contains two other structural domains. From Lim et al.150 Courtesy of F. S. Mathews.

Iron-sulfur clusters are found in flavoproteins such as NADH dehydrogenase (Chapter 18) and trimethylamine dehydrogenase (Fig. 15-9) and in the siroheme-containing sulfite reductases and nitrite reductases.312 These two reductases are found both in bacteria and in green plants. 

The next two entries to Table 3 are cited for completeness. Nitrogenase is treated in Chapter 7 and CO dehydrogenase in Chapter 9. Nitrogenase contains a very complex iron-sulfur cluster that includes another metal, molybdenum or vanadium. The crystal structure of the Mo variant has been determined. There is a third variant, alternative nitrogenase [92], whose cluster apparently does not contain any heterometal. That cluster would thus be a perfect candidate for our definition of a redox-catalytic iron-sulfur cluster. Unfortunately, this third nitrogenase has thus far been characterized to a much lesser extent than the other two forms. For all nitrogenases holds that the binding of N2 to the cluster has not been established [53] therefore, formally these enzymes have not yet been positively identified as redox iron-sulfur catalysts. 

FIGURE 10. Stereo diagram of domain 1 of trimethylamine dehydrogenase. Residues ln371 are shown. Helices aj-ttg of the PgtXg TIM barrel are indicated. The iron sulfur cluster-binding loop consisting of an a-helix and a P-strand is located at the end of helix Og. 

Two clusters in CO dehydrogenase are required for oxidation of CO or reduction of CO 2 (Figure 1). The catalytic site is a nickel iron sulfur cluster called Cluster C. The two electrons involved in this redox reaction are transferred to or from a ferredoxin-like [4Fe64S] cluster called Cluster B. Cluster C is a NiFeS center whereas. Cluster B is most certainly a typical [4Fe64S] cluster (Ragsdale et ah, 1982 Lindahl et al., 1990 Lindahl et ah, 1990). 

As indicated in Sections 1 and 2, succinate is an electron donor widely utilized for NAD(P) reduction by phototrophic purple bacteria. The membrane-bound enzyme responsible for succinate oxidation has been solubilized and partially characterized in the purple non-sulfur bacteria R. rubrum [73,74] and Rhodopseudo-monas sphaeroides (recently renamed Rhodobacter sphaeroides) [57]. In situ characterization of the iron-sulfur centers likely to be associated with succinate dehydrogenase has been accomplished for Rps. capsulata [59] and C. vinosum [51]. Of particular interest is the presence of a succinate-reducible [51,57,58,73] and fu-marate-oxidizable [51] iron-sulfur cluster with near +50 mV that, like center S-3 [60,61,75,76] of mitochondrial succinic dehydrogenase (Complex II), is paramagnetic in the oxidized state. The enzyme in phototrophic bacteria also appears to have one or two ferredoxin-like (i.e., paramagnetic in the reduced state) iron-sulfur centers that correspond to centers S-1 (succinate-reducible, EJ ranging from... 

As discussed in Section IIIC, it has been suggested that the nickel site in carbon monoxide dehydrogenases is associated with an iron-sulfur cluster 266). Possible geometries include a mixed-metal cubane, [Ni-3Fe-4S] and a sulfur-bridged assembly (Fig. 60). A synthetic [Ni-3Fe-4S] cluster has been characterized and its Mossbauer properties are very similar to those of CODH from C. thermoaceticum 86). 

In contrast to the flavin oxidases, flavin dehydrogenases pass electrons to carriers within electron transport chains and the flavin does not react with O2. Examples include a bacterial trimethylamine dehydrogenase (Fig. 15-9) which contains an iron-sulfur cluster that serves as the immediate electron accep-tori67 169 yeast flavoc3Ttochrome hj/ a lactate dehydrogenase that passes electrons to a built-in heme group which can then pass the electrons to an external acceptor, another heme in cytochrome Fike... 

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