title: QM/MM modeling of compound I active species in cytochrome P450, cytochrome C peroxidase, and ascorbate peroxidase.
abstract: QM/MM calculations provide a means for predicting the electronic structure of the metal center in metalloproteins. Two heme peroxidases, Cytochrome c Peroxidase (CcP) and Ascorbate Peroxidase (APX), have a structurally very similar active site, yet have active intermediates with very different electronic structures. We review our recent QM/MM calculations on these systems, and present new computational data. Our results are in good agreement with experiment, and suggest that the difference in electronic structure is due to a large number of small differences in structure from one protein to another. We also discuss recent QM/MM calculations on the active species of cytochrome P450, in which a similar sensitivity of the electronic structure to the environment is found. However, this does not appear to explain different catalytic profiles of the different drug-metabolizing isoforms of this class of enzyme.
authors.affiliation: School of Chemistry and Centre for Computational Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, United Kingdom. Jeremy.Harvey@bristol.ac.uk
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Harvey
authors.forename: Christine M
authors.initials: CM
authors.lastname: Bathelt
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mulholland
mesh_terms: D060387:Ascorbate Peroxidases; D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D003578:Cytochrome-c Peroxidase / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D003577:Cytochrome P-450 Enzyme System; D007501:Iron; D010544:Peroxidases; D060387:Ascorbate Peroxidases; D003578:Cytochrome-c Peroxidase