title: Peroxisome Proliferator-activated Receptors as Potential Targets for Carcinogenic Activity of Polychlorinated Biphenyls: A Computational Perspective.
abstract: Polychlorinated biphenyls (PCBs) are ubiquitous environment-contaminating synthetic chemicals that have been associated with increased risk of hepatic cancer, melanoma, non-Hodgkin lymphoma and cancer of many other body organs. Structural binding analyses of PCB 77 and PCB 118 with peroxisome proliferator-activated receptors (PPARα, PPARβ/δ and PPARγ) was performed to predict the association of PCBs with potential disruption of PPAR signaling pathways.
  
  
  
  The crystal structures of human PPARα, PPARβ/δ and PPARγ were obtained from the Protein Data Bank. Structures of PCB 77 and PCB 118 were obtained from PubChem database. Docking was performed using glide (Schrodinger) induced fit docking (IFD) module.
  
  
  
  The PCB 77 and PCB 118 interacted with PPARα, PPARβ/δ and PPARγ showing an overlapping of 40-58% interacting amino acid residues with synthetic co-complex agonists of the three PPARs. The binding affinity was higher for PCB 118 than for PCB 77 during docking interactions with each of the three PPARs.
  
  
  
  The consistent commonality of interacting residues for PCB 77 and PCB 118 with co-complex synthetic agonists of the PPARs together with good binding affinity suggested that the PPAR signaling pathway is a potential target for toxicologic activity of PCBs.
authors: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia iasheikh@kau.edu.sa.
authors: Ishfaq Ahmad
authors: IA
authors: Sheikh
authors: Department of Biology and Biochemistry, Birzeit University, Birzeit, West Bank, Palestine.
authors: Arwa Abu
authors: AA
authors: Khweek
authors: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors: Mohd Amin
authors: MA
authors: Beg
mesh_terms: D002273:Carcinogens / Q000633:toxicity*; D006801:Humans; D062105:Molecular Docking Simulation; D047492:Peroxisome Proliferator-Activated Receptors / Q000737:chemistry / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011487:Protein Conformation; D015398:Signal Transduction
chemical_list: D002273:Carcinogens; D047492:Peroxisome Proliferator-Activated Receptors; D011078:Polychlorinated Biphenyls
keywords: Docking; PCB 118; PCB 77; PPARα; PPARβ/δ; PPARγ