ABSTRACT

Iron-sulfur clusters are small inorganic entities necessary for the activities of enzymes whose activities are essential to the life-sustaining processes of respiration, nitrogen fixation and photosynthesis. One of the most important roles of iron-sulfur clusters is to serve as agents of the electron transfer reactions necessary for many biological processes. Several proteins required for formation of iron-sulfur clusters have recently been identified and they are among the most conserved proteins found in living cells. These proteins have been designated IscU, IscS, IscA, HscB, HscA, and Fdx. This project is designed to determine how these proteins work together to combine inorganic iron and sulfur to create the clusters. Purified proteins will be used to duplicate the cellular process in vitro and the physiological and biochemical consequences of impairing the function of each protein in vivo will be assessed. In nitrogen-fixing cells there is also a specialized set of homologous proteins that specifically target iron-sulfur cluster formation for the activation of nitrogenase. This project will also involve analysis of these proteins to determine how they target iron and sulfur for the support of biological nitrogen fixation. How iron-sulfur clusters are formed biologically is important because free inorganic iron and free sulfur are metabolic poisons. Furthermore, cellular defects in an ability to properly form iron-sulfur clusters is known to have a profound effect on the metabolism of iron, which can be manifested in a variety of debilitating genetic disorders. Finally, the controlled manipulation of metabolic pathways by altering or increasing the cellular capacity for iron-sulfur cluster formation could have practical application in increasing crop yield, the prevention or treatment of microbial pathogenesis, as well as improving the capacity for certain microoganism to serve as agents of bioremediation.

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