title: LOX1 inhibition with small molecules.
abstract: Lipoxygenases (LOXs) are nonheme, iron-containing dioxygenases that catalyze the dioxygenation of polyunsaturated fatty acids and are widely distributed among plant and animal species. Human LOXs, now identified as key enzymes in the pathogenesis of major disorders, have increasingly drawn the attention as targets and great effort has been made for the discovery and design of suitable inhibitors, to which end both pharmacological and computational methods have been employed. In the present work, using pharmacophore modeling and docking, we attempt to elucidate the inhibition of LOX1 with a new inhibitor, albidoside, an iridoid glucoside isolated from plants of the Scutellaria genus. Through a pharmacophore approach, complementarities between the ligand and the binding site are explored and a plausible mode of binding with the protein is suggested for albidoside.
authors.affiliation: Department of Chemistry, Technical University of Denmark, DK-2800 Lyngby, Denmark. Electronic address: chgou@kemi.dtu.dk.
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Gousiadou
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.
authors.forename: Irene
authors.initials: I
authors.lastname: Kouskoumvekaki
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D057927:Hydrophobic and Hydrophilic Interactions; D039823:Iridoids / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D008084:Lipoxygenase / Q000737:chemistry*; D016859:Lipoxygenase Inhibitors / Q000737:chemistry*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010940:Plant Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D054852:Small Molecule Libraries / Q000737:chemistry*; D013025:Glycine max / Q000737:chemistry* / Q000201:enzymology; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D039823:Iridoids; D008024:Ligands; D016859:Lipoxygenase Inhibitors; D010940:Plant Proteins; D054852:Small Molecule Libraries; D008084:Lipoxygenase
keywords: Docking; Inhibition; Iridoids; Lipoxygenases; Pharmacophore