| Abstract
| - Peroxidases are oxidative metabolizing heme proteins that requirehydrogen peroxide to be transformedto the catalytically active, compound I, species from theferric resting state. Although a peroxide complex hasbeenproposed as a key intermediate in this reaction, this intermediate istoo transient to have thus far been definitivelycharacterized. Results of previous molecular dynamics (MD)simulations of a peroxide complex with cytochromeC peroxidase (CCP) indicated that peroxide forms a stable complex andbinds in a nonsymmetric, end-on mode inwhich the oxygen atoms systematically exchange places as ligands forthe iron. These results provided support fora plausible pathway from the peroxide complex to compound I,involving the participation of nearby histidine andarginine residues. To further explore the reliability of thisbonding description, we report here, for the first time,theuse of ab initio methods to determine the optimized geometry andstability of a peroxide complex with a modelheme peroxidase. Two stable minima were identified, with bindingenergies of 9.7 kcal/mol. In both of thesecomplexes, the peroxide binds in an end-on mode but with alternativeoxygen atoms as the Fe ligand. No minimumcorresponding to a bridged structure could be found. The twoend-on minima are connected by a low-energy ridge.These results provide confirmation of three mechanisticallyimportant characteristics found in the previous 300 KMD simulations of a peroxidase−HOOH complex: (i) formation of astable peroxide complex, (ii) binding of peroxidein an asymmetric end-on mode, and (iii) dynamic interchange between theoxygen atoms that bind to the Fe, implyinga small energy barrier between them.
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