title: Homology models of human all-trans retinoic acid metabolizing enzymes CYP26B1 and CYP26B1 spliced variant.
abstract: Homology models of CYP26B1 (cytochrome P450RAI2) and CYP26B1 spliced variant were derived using the crystal structure of cyanobacterial CYP120A1 as template for the model building. The quality of the homology models generated were carefully evaluated, and the natural substrate all-trans-retinoic acid (atRA), several tetralone-derived retinoic acid metabolizing blocking agents (RAMBAs), and a well-known potent inhibitor of CYP26B1 (R115866) were docked into the homology model of full-length cytochrome P450 26B1. The results show that in the model of the full-length CYP26B1, the protein is capable of distinguishing between the natural substrate (atRA), R115866, and the tetralone derivatives. The spliced variant of CYP26B1 model displays a reduced affinity for atRA compared to the full-length enzyme, in accordance with recently described experimental information.
authors.affiliation: Computational Chemistry and Biology Group, Facultad de Química, UdelaR, 11800 Montevideo, Uruguay.
authors.forename: Patricia
authors.initials: P
authors.lastname: Saenz-Méndez
authors.forename: Ali Ateia
authors.initials: AA
authors.lastname: Elmabsout
authors.forename: Helena
authors.initials: H
authors.lastname: Sävenstrand
authors.forename: Mohamed Khalid Alhaj
authors.initials: MK
authors.lastname: Awadalla
authors.forename: Åke
authors.initials: Å
authors.lastname: Strid
authors.forename: Allan
authors.initials: A
authors.lastname: Sirsjö
authors.forename: Leif A
authors.initials: LA
authors.lastname: Eriksson
mesh_terms: D017398:Alternative Splicing; D001426:Bacterial Proteins / Q000737:chemistry*; D052160:Benzothiazoles / Q000737:chemistry; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry; D062105:Molecular Docking Simulation; D000072516:Retinoic Acid 4-Hydroxylase; D040681:Structural Homology, Protein; D046939:Synechocystis / Q000737:chemistry* / Q000201:enzymology; D044024:Tetralones / Q000737:chemistry; D013816:Thermodynamics; D014212:Tretinoin / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D052160:Benzothiazoles; C500480:CYP120A1 protein, Synechocystis; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D044024:Tetralones; D014230:Triazoles; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607079:CYP26B1 protein, human; D000072516:Retinoic Acid 4-Hydroxylase; C406527:R 115866