Synthetic active site analogues of heme-thiolate proteins. Characterization and identification of intermediates of the catalytic cycles of cytochrome P450cam and chloroperoxidase.
In view of recent results from different sources, the reaction mechanisms of two heme-thiolate proteins, cytochrome P450cam and chloroperoxidase (CPO), are discussed. In this context a mechanism of CPO is proposed which includes H2O2 cleavage, subsequent formation of compound I and the identification of two elusive intermediates. The HOCl adduct of the iron(III)porpyhrin is the catalytically competent Cl+ donor chlorinating activated C-H bonds of substrates bound to the enzyme. Pulse-EPR characterization of an enzyme model of the resting state of P450cam suggests a role of the electric field of the protein for stabilizing the low-spin state of the cofactor of the enzyme. It is further suggested that the same effect of the protein may trigger the reactivity of compound I such that both concerted and two-step reactions are feasible within the concept of a Two-State-Reactivity. This review emphasizes the value of synthetic enzyme models complementing investigations of the native proteins.
Woggon
W D
WD
Institute of Organic Chemistry, University of Basel, Switzerland. wolf-d.woggon@unibas.ch
Wagenknecht
H A
HA
Claude
C
C
D001665:Binding Sites; D019475:Camphor 5-Monooxygenase / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D002711:Chloride Peroxidase / Q000737:chemistry* / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds
D002712:Chlorides; D013438:Sulfhydryl Compounds; D006418:Heme; D006861:Hydrogen Peroxide; D002711:Chloride Peroxidase; D019475:Camphor 5-Monooxygenase