title: Computational insights into the molecular interactions of environmental xenoestrogens 4-tert-octylphenol, 4-nonylphenol, bisphenol A (BPA), and BPA metabolite, 4-methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene (MBP) with human sex hormone-binding globulin.
abstract: Environmental contamination has been one of the major drawbacks of the industrial revolution. Several man-made chemicals are constantly released into the environment during the manufacturing process and by leaching from the industrial products. As a result, human and animal populations are exposed to these synthetic chemicals on a regular basis. Many of these chemicals have adverse effects on the physiological functions, particularly on the hormone systems in human and animals and are called endocrine disrupting chemicals (EDCs). Bisphenol A (BPA), 4-tert-octylphenol (OP), and 4-nonylphenol (NP) are three high volume production EDCs that are widely used for industrial purposes and are present ubiquitously in the environment. Bisphenol A is metabolized in the human body to a more potent compound (MBP: 4-Methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene). Epidemiological and experimental studies have shown the three EDCs to be associated with adverse effects on reproductive system in human and animals. Sex hormone-binding globulin (SHBG) is a circulatory protein that binds sex steroids and is a potential target for endocrine disruptors in the human body. The current study was done in order to understand the binding mechanism of OP, BPA, NP, and MBP with human SHBG using in silico approaches. All four compounds showed high binding affinity with SHBG, however, the binding affinity values were higher (more negative) for MBP and NP than for OP and BPA. The four ligands interacted with 19-23 residues of SHBG and a consistent overlapping of the interacting residues for the four ligands with the residues for the natural ligand, dihydrotestosterone (DHT; 82-91% commonality) was shown. The overlapping SHBG interacting residues among DHT and the four endocrine disruptors suggested that these compounds have potential for interference and disruption in the steroid binding function.
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Ishfaq A
authors.initials: IA
authors.lastname: Sheikh
authors.affiliation: Faculty of Computing and Information Technology, King Abdulaziz University, Rabigh, Kingdom of Saudi Arabia.
authors.forename: Iftikhar A
authors.initials: IA
authors.lastname: Tayubi
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Ejaz
authors.initials: E
authors.lastname: Ahmad
authors.affiliation: College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Kingdom of Saudi Arabia.
authors.forename: Majid A
authors.initials: MA
authors.lastname: Ganaie
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Osama S
authors.initials: OS
authors.lastname: Bajouh
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Samera F
authors.initials: SF
authors.lastname: AlBasri
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Ibtihal M J
authors.initials: IMJ
authors.lastname: Abdulkarim
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. Electronic address: mabeg51@gmail.com.
authors.forename: Mohd A
authors.initials: MA
authors.lastname: Beg
mesh_terms: D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D013196:Dihydrotestosterone / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004785:Environmental Pollutants / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D010636:Phenols / Q000494:pharmacology*; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects* / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D013196:Dihydrotestosterone; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004967:Estrogens; D008024:Ligands; D010636:Phenols; D012738:Sex Hormone-Binding Globulin; C504750:4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene; C041594:4-nonylphenol; C105260:4-tert-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Docking; Endocrine disruption; Nonylphenol; Octylphenol; Sex hormone-binding globulin