title: Structural basis of substrate conversion in a new aromatic peroxygenase: cytochrome P450 functionality with benefits.
abstract: 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 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.
authors.affiliation: From the Institute of Organic Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg.
authors.forename: Klaus
authors.initials: K
authors.lastname: Piontek
authors.forename: Eric
authors.initials: E
authors.lastname: Strittmatter
authors.forename: René
authors.initials: R
authors.lastname: Ullrich
authors.forename: Glenn
authors.initials: G
authors.lastname: Gröbe
authors.forename: Marek J
authors.initials: MJ
authors.lastname: Pecyna
authors.forename: Martin
authors.initials: M
authors.lastname: Kluge
authors.forename: Katrin
authors.initials: K
authors.lastname: Scheibner
authors.forename: Martin
authors.initials: M
authors.lastname: Hofrichter
authors.forename: Dietmar A
authors.initials: DA
authors.lastname: Plattner
mesh_terms: D055362:Agrocybe / Q000737:chemistry* / Q000201:enzymology; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D010084:Oxidation-Reduction; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C022333:peroxygenase
keywords: Cytochrome P450; Fungi; Glycoprotein; Heme; Magnesium; Oxyfunctionalization; Peroxygenase; Polycyclic Aromatic Hydrocarbons