Does P450-type catalysis proceed through a peroxo-iron intermediate? A review of studies with microperoxidase.
Recent stopped-flow kinetics demonstrated the existence of an intermediate before the occurrence of the final product of the reaction of both iron-containing microperoxidase-8 (Fe(III)MP-8) and manganese-containing microperoxidase-8 (Mn(III)MP-8) with H(2)O(2). The intermediate was assigned to be (hydro)peroxo-iron. With both mini-catalysts the final state obtained after 30-40 ms showed a resemblance to PorM(IV)MP-8[double bond]O(R(+)*); (R(+)*) is a radical located at the peptide. Quantum mechanical calculations indicate that hydroperoxo-iron is inactive as a catalytic intermediate in cytochrome P450 (P450)-type catalysis. Instead, the calculations suggest that peroxo-iron acts as the catalytic intermediate in P450-type catalysis. In addition, the calculations demonstrate that, although less likely, the possibility that oxenoid-iron acts as a catalytic intermediate in P450 catalysis cannot be fully excluded. An interesting aspect of the reactions catalysed by MP-8 is the possibility that, in view of the reversibility of the reactions between (hydro)peroxo-iron and oxenoid-iron, H(2)O plays a decisive role, at least in some cytochromes P450, in the removal of halogens, avoiding the production of compounds hazardous to the organism.
Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen, The Netherlands. cees.veeger@planet.nl
Cees
C
Veeger
D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D003574:Cytochrome c Group / Q000737:chemistry / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D010544:Peroxidases / Q000737:chemistry* / Q000378:metabolism
D003574:Cytochrome c Group; D009842:Oligopeptides; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D007501:Iron; D010544:Peroxidases; C021799:microperoxidase; D010100:Oxygen