Structural basis of substrate conversion in a new aromatic peroxygenase: cytochrome P450 functionality with benefits

J Biol Chem. 2013 Nov 29;288(48):34767-76. doi: 10.1074/jbc.M113.514521. Epub 2013 Oct 14.


Aromatic peroxygenases (APOs) represent a unique oxidoreductase sub-subclass of heme proteins with peroxygenase and peroxidase activity and were thus recently assigned a distinct EC classification (EC 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.

Keywords: Cytochrome P450; Fungi; Glycoprotein; Heme; Magnesium; Oxyfunctionalization; Peroxygenase; Polycyclic Aromatic Hydrocarbons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agrocybe / chemistry*
  • Agrocybe / enzymology
  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray*
  • Cytochrome P-450 Enzyme System / chemistry
  • Mixed Function Oxygenases / chemistry*
  • Mixed Function Oxygenases / metabolism
  • Molecular Docking Simulation
  • Oxidation-Reduction
  • Polycyclic Aromatic Hydrocarbons / chemistry*
  • Polycyclic Aromatic Hydrocarbons / metabolism
  • Protein Conformation
  • Substrate Specificity


  • Polycyclic Aromatic Hydrocarbons
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • peroxygenase

Associated data

  • PDB/2YOR
  • PDB/2YP1