PMID- 27281544 OWN - NLM STAT- MEDLINE DCOM- 20170306 LR - 20181202 IS - 1879-1298 (Electronic) IS - 0045-6535 (Linking) VI - 159 DP - 2016 Sep TI - Mechanisms of interaction between persistent organic pollutants (POPs) and CYP2B6: An in silico approach. PG - 113-125 LID - S0045-6535(16)30697-X [pii] LID - 10.1016/j.chemosphere.2016.05.049 [doi] AB - Human Cytochrome P450s (CYP450) are a group of heme-containing metalloenzymes responsible for recognition and metabolism of numerous xenobiotics, including drugs and environmental contaminants. CYP2B6, a member of CYP450, is well known for being a highly inducible and polymorphic enzyme and for its important role in the oxidative metabolism of environmental pollutants, such as the Polybrominated Diphenyl Ethers (PBDEs) and Polychlorinated Biphenyls (PCBs). However the mechanisms of interaction of PBDEs and PCBs with CYP2B6 is not entirely known. In this work, a computational approach was carried out to study the interactions of 41 POPs (17 PBDEs, 17 PCBs, and 7 Dioxins) with four CYP2B6 protein structures downloaded from PDB data base (PDB: 3UA5, 3QOA, 3QU8 and 4I91) using molecular docking protocols with AutoDock Vina. The best binding affinity values (kcal/mol) were obtained for PBDE-99 (-8.5), PCB-187 (-9.6), and octachloro-dibenzo-dioxin (-9.8) that can be attributed to the hydrophobic interactions with important residues, such as Phe-363, in the catalytic site of CYP2B6. Molecular docking validation revealed the best values for PDB: 3UA5 (R = 0.622, p = 0.001) demonstrating the reliability of molecular docking predictions. The information obtained in this work can be useful in evaluating the modes of interaction of xenobiotic compounds with the catalytic site of CYP2B6 and provide insights on the important role of these enzymes in the metabolism of potentially toxic compounds in humans. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Maldonado-Rojas, Wilson AU - Maldonado-Rojas W AD - Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, 130014 Cartagena, Colombia. FAU - Rivera-Julio, Karen AU - Rivera-Julio K AD - Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, 130014 Cartagena, Colombia. FAU - Olivero-Verbel, Jesus AU - Olivero-Verbel J AD - Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, 130014 Cartagena, Colombia. Electronic address: joliverov@unicartagena.edu.co. FAU - Aga, Diana S AU - Aga DS AD - Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA. LA - eng PT - Journal Article DEP - 20160607 PL - England TA - Chemosphere JT - Chemosphere JID - 0320657 RN - 0 (Dioxins) RN - 0 (Environmental Pollutants) RN - 0 (Halogenated Diphenyl Ethers) RN - DFC2HB4I0K (Polychlorinated Biphenyls) RN - EC 1.14.14.1 (Cytochrome P-450 CYP2B6) SB - IM MH - Cytochrome P-450 CYP2B6/*metabolism MH - Dioxins/*metabolism MH - Environmental Pollutants/*metabolism MH - Halogenated Diphenyl Ethers/*metabolism MH - Humans MH - Molecular Docking Simulation MH - Polychlorinated Biphenyls/*metabolism MH - Reproducibility of Results OTO - NOTNLM OT - AutoDock Vina OT - Environmental pollutant OT - Molecular docking OT - Xenobiotic EDAT- 2016/06/10 06:00 MHDA- 2017/03/07 06:00 CRDT- 2016/06/10 06:00 PHST- 2015/11/12 00:00 [received] PHST- 2016/04/14 00:00 [revised] PHST- 2016/05/17 00:00 [accepted] PHST- 2016/06/10 06:00 [entrez] PHST- 2016/06/10 06:00 [pubmed] PHST- 2017/03/07 06:00 [medline] AID - S0045-6535(16)30697-X [pii] AID - 10.1016/j.chemosphere.2016.05.049 [doi] PST - ppublish SO - Chemosphere. 2016 Sep;159:113-125. doi: 10.1016/j.chemosphere.2016.05.049. Epub 2016 Jun 7.