The fundamental, versatile role of diiron enzymes in lipid metabolism

Diiron enzymes catalyze many essential O2-dependent reactions required for eukaryotic and bacterial metabolism. Both membrane bound and soluble classes are now known. The integral membrane class of diiron enzymes contains desaturases, hydroxylases, and other oxidative enzymes involved in the synthesis of nutritionally or commercially desirable unsaturated fats, steroids, and other hydrophobic molecules. The soluble class of diiron enzymes has essential roles in DNA biosynthesis, desaturation of various acyl-ACPs, and the oxidation of hydrocarbons including toxic environmental pollutants. Biochemical, spectroscopic, and crystallographic studies of these enzymes have provided structures for the active sites and proposals for the mechanism of action. Two key features of the reaction cycles are the flexibility of the diiron coordination environment and the activation of O2 to generate a series of related but not identical intermediates used for diverse catalytic processes. Most recently, the alpha helical bundle containing the diiron center has proven to be a robust scaffold for mutagenesis studies, allowing the relationship between protein structure and catalytic function to be further refined and adapted.