Structural Basis of Substrate Conversion in a New Aromatic Peroxygenase

Klaus Piontek, Eric Strittmatter, René Ullrich, Glenn Gröbe, Marek J. Pecyna, Martin Kluge, Katrin Scheibner, Martin Hofrichter, Dietmar A. Plattner
2013 Journal of Biological Chemistry  
Aromatic peroxygenases (APOs) are the "missing link" between heme peroxidases and P450-monooxygenases. Results: Based on two crystal structures the substrate conversion of APOs is elucidated. Conclusion: The specific design of the heme cavity and the distal heme access channel govern substrate specificity. Significance: APOs can be utilized in biotechnology and organic synthesis having significant advantages when compared with cytochrome P450 enzymes. Aromatic peroxygenases (APOs) represent a
more » ... ique oxidoreductase sub-subclass of heme proteins with peroxygenase and peroxidase activity and were thus recently assigned a distinct EC classification (EC 1.11.2.1). They catalyze, inter alia, oxyfunctionalization reactions of aromatic and aliphatic hydrocarbons with remarkable regio-and stereoselectivities. When compared with cytochrome P450, APOs appear to be the choice enzymes for oxyfunctionalizations in organic synthesis due to their independence from a cellular environment and their greater chemical versatility. Here, the first two crystal structures of a heavily glycosylated fungal aromatic peroxygenase (AaeAPO) are described. They reveal different pH-dependent ligand binding modes. We model the fitting of various substrates in AaeAPO, illustrating the way the enzyme oxygenates polycyclic aromatic hydrocarbons. Spatial restrictions by a phenylalanine pentad in the active-site environment govern substrate specificity in AaeAPO.
doi:10.1074/jbc.m113.514521 pmid:24126915 pmcid:PMC3843090 fatcat:3ai2clw22rfxbeg5ipe5s63n2y