Diiron-cluster intermediates in biological oxygen activation reactions

Abstract

The activation of molecular oxygen is a fundamental process that is important in metabolic reactions in biological systems. In addition to the well-studied role of hemoproteins in participating in oxygen activation, there is increasing evidence that dinuclear iron centers in proteins also function in this role. Recent work on the interaction of the dinuclear iron centers found in ribonucleotide reductase and in methane monooxygenase with molecular oxygen is reviewed. Available spectroscopic data on reaction intermediates trapped by the rapid freeze quench kinetic technique allow insights into their structures and on the oxidation level of each Fe ion in the complex. These data suggest the initial intermediate formed on reaction of the diferrous center with oxygen is the formation of a diferric peroxo complex which undergoes further internal electron reorganization to form a diferryl-oxo complex termed intermediate Q. It is suggested that these intermediates are formed as initial steps in both methane monooxygenase and in ribonucleotide reductase activation of molecular oxygen. Further reaction steps of Q in each enzyme are distinguished by the source of the subsequent reducing equivalent. In the case of methane monooxygenase, the hydrocarbon substrate is the source of the required reducing equivalent to form a mixed valent ferryl/ferric complex which is proposed to donate a hydroxyl group to the hydrocarbon radical with resulting formation of a diferric ‘resting’ state and product. An external electron source supplies the single electron to the difrrryl center in ribonucleotide reductase to form a mixed valent complex that is capable of oxidizing a proximal tyrosyl residue (122) to its stable radical form with formation of the ‘resting’ diferric form of the enzyme. This ‘unified’ scheme for the activation of molecular oxygen by dinuclear iron centers in these two enzymes may have applicability to other enzymes containing these centers.