Iron-sulfur clusters definition

A more specific operational definition excludes the unique clusters of the nitrogenase enzymes (which are treated in Chapter 7) from our considerations biological iron-sulfur clusters in this context only deal with Fe and do not contain any other metal. Under physiological conditions they can occur in two, and not more than two, oxidation states. All clusters are either dinuclear or one of the... 

Several other possible biological functions of iron-sulfur clusters have been proposed as summarized in Table 1. Let us briefly discuss this list in detail to indicate why the majority of the entries are excluded from our definition of catalytic iron-sulfur clusters. 

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. 

Rare examples of unique topologies in such systems are known. However, it was recently realized that when the analysis includes cofactors and prosthetic groups such as seen in quinoproteins or iron-sulfur cluster proteins, interesting topologies including knots and catenanes are in fact more common than previously realized. As always, in considering stereochemical phenomena, our definition of connectivity is crucial. Earlier studies had counted only the amino acids as contributing to the connectivity of the system. When cofactors are included, more complex connectivities result. 

The problem with the application of fliis principle in proteins is spectral crowding for proton interactions and, combined with this, only partial definition of hyperfine lines over the whole range of flie EPR spectrum. This makes direct tensor determination somewhat ambiguous, but in connection with known molecular stractures a unique solution can typically be found. A very important asset in this respect is site-directed mutagenesis, by which specific amino acid residues can be changed. For most of the examples of iron-sulfur clusters discussed, a full analysis was possible even without this tool. 

One of the earliest successful applications of EXAFS to probe a me-talloenzyme was the study of the molybdenum site of nitrogenase. Studies were made on both the C. pasteurianum and A. vinelandii MoFe-proteins and on isolated FeMoco (116). These studies showed definitively that molybdenum is present as part of a polynuclear cluster containing sulfur and iron, with Mo—S and Mo—Fe distances of —2.36 and —2.72 A, respectively. This work inspired the successful development of many chemical systems containing Mo—Fe—S clusters, and XAS studies of these systems strengthened the basis for the interpretation of corresponding data for the natural system. The most accurate picture of the molybdenum site of FeMoco currently available involves a coordination of about three oxygen (or nitrogen), sulfur, and iron atoms at —2.10, —2.37, and —2.70 A, respectively (117). 

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