[Fe-S] containing enzymes

Many processes associated with DNA synthesis and repair, involve metal-containing cofactors, and misregulation of these processes can lead to carcinogenesis. However, because of the paucity of biochemical and structural information, knowledge of their modi operandi or the molecular linkage between integrity of the metallocofactor and pathological events remain largely unknown. A particularly important class of metal cofactors is that of iron-sulfur [Fe-S] clusters, perhaps the most ubiquitous prosthetic groups in nature. Their abundance is likely the consequence of their structural and redox plasticity, thereby making them versatile and tunable cofactors for mediating electron transfer. However, [Fe-S]-cluster containing proteins are much more functionally versatile than that originally thought; they mediate and participate in a variety of cellular processes, such as DNA maintenance, amino acid and nucleotide metabolism, ribosome function and tRNA modification. [Fe-S] clusters participate in enzyme catalysis and bind substrates, regulate gene expression, act as sensors of small molecules (i.e. O2, NO), store iron, serve as sulfur donors during synthesis of lipoic acid and biotin, etc. Thus, despite the simplicity of their chemical ‘make-up’, their chemical and functional diversity is both astounding and complex.