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Molecules 2016, 21(3), 351; doi:10.3390/molecules21030351

Improved Homology Model of the Human all-trans Retinoic Acid Metabolizing Enzyme CYP26A1

1
Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, P. O. Box 2440, 81451 Hail, Saudi Arabia
2
Department of Clinical Pharmacology, College of Pharmacy, University of Hail, P. O. Box 2440, 81451 Hail, Saudi Arabia
3
Department of Chemistry and Molecular Biology, University of Gothenburg, 40530 Gothenburg, Sweden
4
Computational Chemistry and Biology Group, Facultad de Química, UdelaR, 11800 Montevideo, Uruguay
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 17 February 2016 / Revised: 7 March 2016 / Accepted: 9 March 2016 / Published: 15 March 2016
(This article belongs to the Special Issue Computational Design: A New Approach to Drug and Molecular Discovery)
View Full-Text   |   Download PDF [7066 KB, uploaded 15 March 2016]   |  

Abstract

A new CYP26A1 homology model was built based on the crystal structure of cyanobacterial CYP120A1. The model quality was examined for stereochemical accuracy, folding reliability, and absolute quality using a variety of different bioinformatics tools. Furthermore, the docking capabilities of the model were assessed by docking of the natural substrate all-trans-retinoic acid (atRA), and a group of known azole- and tetralone-based CYP26A1 inhibitors. The preferred binding pose of atRA suggests the (4S)-OH-atRA metabolite production, in agreement with recently available experimental data. The distances between the ligands and the heme group iron of the enzyme are in agreement with corresponding distances obtained for substrates and azole inhibitors for other cytochrome systems. The calculated theoretical binding energies agree with recently reported experimental data and show that the model is capable of discriminating between natural substrate, strong inhibitors (R116010 and R115866), and weak inhibitors (liarozole, fluconazole, tetralone derivatives). View Full-Text
Keywords: CYP26A1; homology model; RAMBA; retinoic acid; molecular docking CYP26A1; homology model; RAMBA; retinoic acid; molecular docking
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Awadalla, M.K.A.; Alshammari, T.M.; Eriksson, L.A.; Saenz-Méndez, P. Improved Homology Model of the Human all-trans Retinoic Acid Metabolizing Enzyme CYP26A1. Molecules 2016, 21, 351.

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