Iron Proteins with Dinuclear Active Sites

Abstract

AbstractIron proteins with dinuclear active sites include those containing stable nonheme, non‐sulfur diiron sites. Though still dwarfed by the numbers of heme or iron‐sulfur proteins, the list of proteins known to contain nonheme, non‐sulfur diiron sites has steadily expanded over the past thirty years. These proteins share the following active site properties: (1) two iron atoms separated by 4 Å or less; (2) stable high spin ferrous and ferric oxidation states; (3) terminal histidinyl imidazole, carboxylate and solvent ligands; (4) at least one ligand that bridges the two irons; and (5) magnetic superexchange coupling of the unpaired spins on the two irons mediated by the bridging ligand atom(s). With one possible exception, the bridging ligands are either known or are strongly suspected to include one or two carboxylates. Two distinct subclasses, the purple acid phosphatases and the flavo‐diiron enzymes, seem to have no structural or functional relationships to each other or to any of the other diiron enzymes. The oxygen‐carrying protein, hemerythrin, for many years served as the prototype for nonheme, non‐sulfur diiron proteins. However, its structure and function have turned out to be distinct from those of the O2‐activating enzymes, which now form the largest subclass of these diiron‐containing proteins, with at least seven distinct types known; the most numerous of these are the alkane (including methane) monooxygenases and fatty acyl desaturases. Evidence for catalytically competent high‐valent diiron intermediates resulting from reaction of the diferrous sites with dioxygen have been obtained for at least two of the O2‐activating enzymes. Among the most intriguing and mysterious of the O2‐activating enzymes are the membrane‐bound ‘eight‐His’ diiron desaturases and monooxygenases.