ABSTRACT
The stability of the cluster itself is a totally different issue. By accepting the notion that iron-sulfur clusters are always particularly stable from the coordina tion chemistry point of view, a key role in the stability of the cluster is played by its accessibility to solvent in relation to its oxidation state. From model compounds we learn that some cluster oxidation states are stable in water and some are not. An example of the latter is the [Fe4S4]3+ cluster, which undergoes hydrolysis in water. This cluster exists only in HiPIPs. Indeed, oxidation of ferredoxins to the [Fe4S4]3+ state leads to immediate cluster hydrolysis [186,187]. It is believed that this cluster is stable in HiPIPs because it is shielded from the solvent [35]. Denaturation studies have led to the proposal that reduced HiPIPs, containing the [Fe4S4]2+ cluster, are indefinitely stable, whereas their oxidized forms are not because the protein is fluxional, and from time to time it opens up and exposes the oxidized cluster to the solvent. Addition of increasing amounts of denaturants increases the fraction of protein in the intermediate state discussed above [172] and characterized by a more exposed cluster. Therefore, the fractional amount of time that the protein spends in an opened state increases, and the rate of cluster hydrolysis increases. For the reduced protein, this equilibrium with the intermedi ate solvent-exposed form is harmless, and the initial stages of unfolding can be followed up to the full formation of the intermediate. If the intermediate is oxi dized, instantaneous hydrolysis and loss of the cluster occurs (Fig. 30), just as occurs in ferredoxins.
