Mechanism of Fe-S cluster biosynthesis: the [2Fe-2S] IscU as a model scaffold
Of the transition metals, iron is the metal of choice for cells (with the exception of a few Lactobacillus species) found mainly in heme and Fe-S cofactors. However despite being an essential mineral, iron has the ability to activate dioxygen toward the formation of reactive oxygen species (ROS) capable of damaging biomolecules. As such, maintenance of iron concentrations is crucial. Reconstitution of Fe-S proteins is facile and is comprised of simply incubating the apo protein with excess inorganic iron salts and sulfides in the presence of a reductant such as ?-mercaptoethanol or dithiothreitol (DTT). Because free iron and sulfide are cellulary toxic, accessory proteins are undoubtedly essential for provisions of iron and sulfur equivalents for the maturation of Fe-S proteins. Since first characterized in the 1960s, only recent progress in the last decade has provided insights into understanding Fe-S biosynthesis. Three such systems are known: 1) nif – gene products involved in the maintenance of nitrogenase biosynthesis; 2) isc – homologous to nif and found in both bacteria and eukaryotes; and 3) suf – implicated to be redundant to isc. In this study, IscU serves as a platform for understanding the mechanism of [2Fe-2S] cluster assembly utilizing its substrate IscS, a desulfurase that catalyzes the decomposition of L-Cys to Ala and sulfur equivalents for the IscU scaffold. Both proteins are gene products of the isc (iron sulfur cluster) operon, the topic of the current work.
School:The Ohio State University
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:fe s iron sulfur iscu iscs nifs
Date of Publication:01/01/2004