Mechanisms of interaction between persistent organic pollutants (POPs) and CYP2B6: An in silico approach

Mother to Fetus Transfer of Hydroxylated Polychlorinated Biphenyl Congeners (OH-PCBs) in the Japanese Macaque (Macaca fuscata): Extrapolation of Exposure Scenarios to Humans

“…37 More recently, screening of in silico docking simulations for several human CYP isozymes and PCB congeners suggested that CYP2A6 is involved in CB187 metabolism. 38,39 In addition, CYP1A1, CYP2A6, and CYP2B6 isozymes in human were reported to be involved in the metabolism of PCB congeners. 40 Our results suggest that Japanese macaque has relatively strong CYP2A6 and CYP2B-like activities and can metabolize CB187 to 4OH-CB187.…”

Hepatic Transcriptomic Patterns in the Neonatal Rat After Pentabromodiphenyl Ether Exposure

“…Minimal hepatic centrilobular vacuolization occurred only with the PBDE mixture suggesting that components in the mixture (other than PBDE-47) may be responsible for this lesion. There are reports in the literature that PBDE-99, present in the mixture, may have some transient effects not found with PBDE-47, 77 –79 and this may account for the hepatic lesions with the PBDE mixture exposure. However, after longer term PBDE-47 exposure hepatic toxic lesions occur in rats.…”

Multidisciplinary Insights into the Structure–Function Relationship of the CYP2B6 Active Site

“…While this description of CYP2B6 ligands is useful, many of these characterizations are generalizations due to the sensitivity and variability of the CYP2B6 structure-function relationship. For example, CYP2B6 has difficulty metabolizing planar molecules, yet planar dioxins have been predicted to readily bind and bioaccumulate within the enzyme (Maldonado-Rojas et al, 2016). This observation can be explained, at least in part, by the capacity of halogen atoms in dioxins, other persistent organic pollutants (POPs), and additional CYP2B6 substrates/inhibitors to promote tight ligand binding within CYP2B6 (Korhonen et al, 2007;Maldonado-Rojas et al, 2016;Wang et al, 2019b).…”

“…Specifically, a surplus of in silico information concerning CYP2B6 such as its substrate/inhibitor characteristics (Wang and Halpert, 2002;Korhonen et al, 2007;Ekins et al, 2008;Wang et al, 2019b), 13 crystal structures (Table 1), active site amino acids (Supplemental Table 1 and Table 1), and plasticity (Shah et al, 2012;Wilderman and Halpert, 2012;Shah et al, 2018) has been elucidated. The techniques of quantitative structureactivity relationships (QSARs) (Wang and Halpert, 2002;Lewis et al, 2010;Dmitriev et al, 2021), homology modeling (Lewis et al, 1999;Bathelt et al, 2002;Lewis et al, 2002), X-ray crystallography (Gay et al, 2010;Halpert, 2011;Shah et al, 2018), and molecular docking (Niu Radloff et al, 2013;Maldonado-Rojas et al, 2016) have been pivotal in this endeavor. For a full view of the significant in silico work done with CYP2B6, we have compiled a historical table of CYP2B6 homology models (Supplemental Table 1) and a modern table of CYP2B6 crystal structures/molecular docking results (Table 1) with predicted active site residues around various ligands noted.…”