Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight.
Exposure to toxic industrial chemicals that have capacity to disrupt the endocrine system, also known as endocrine disrupting chemicals (EDCs), has been increasingly associated with reproductive problems in human population. Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) and 4-tert-octylphe...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4574962?pdf=render |
| _version_ | 1818236649375531008 |
|---|---|
| author | Mohd Rehan Ejaz Ahmad Ishfaq A Sheikh Adel M Abuzenadah Ghazi A Damanhouri Osama S Bajouh Samera F AlBasri Mansour M Assiri Mohd A Beg |
| author_facet | Mohd Rehan Ejaz Ahmad Ishfaq A Sheikh Adel M Abuzenadah Ghazi A Damanhouri Osama S Bajouh Samera F AlBasri Mansour M Assiri Mohd A Beg |
| author_sort | Mohd Rehan |
| collection | DOAJ |
| description | Exposure to toxic industrial chemicals that have capacity to disrupt the endocrine system, also known as endocrine disrupting chemicals (EDCs), has been increasingly associated with reproductive problems in human population. Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) and 4-tert-octylphenol (OP; 4-(1,1,3,3-tetramethylbutyl)phenol) are among the most common environmental contaminants possessing endocrine disruption properties and are present in plastics, epoxy resins, detergents and other commercial products of common personal and industrial use. A metabolite of BPA, 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is about 1000 times more biologically active compared to BPA. Epidemiological, clinical, and experimental studies have shown association of BPA and OP with adverse effects on male and female reproductive system in human and animals. The endocrine disruption activity can occur through multiple pathways including binding to steroid receptors. Androgen receptor (AR) and progesterone receptor (PR) are critical for reproductive tract growth and function. Structural binding characterization of BPA, MBP, and OP with AR and PR using molecular docking simulation approaches revealed novel interactions of BPA with PR, and MBP and OP with AR and PR. For BPA, MBP, and OP, five AR interacting residues Leu-701, Leu-704, Asn-705, Met-742, and Phe-764 overlapped with those of native AR ligand testosterone, and four PR interacting residues Leu-715, Leu-718, Met-756, and Met-759 overlapped with those of PR co-complex ligand, norethindrone. For both the receptors the binding strength of MBP was maximum among the three compounds. Thus, these compounds have the potential to block or interfere in the binding of the endogenous native AR and PR ligands and, hence, resulting in dysfunction. The knowledge of the key interactions and the important amino-acid residues also allows better prediction of potential of xenobiotic molecules for disrupting AR- and PR-mediated pathways, thus, helping in design of less potent alternatives for commercial use. |
| first_indexed | 2024-12-12T12:13:13Z |
| format | Article |
| id | doaj.art-ebb8c88da31e400c93d2d55f5c587c2d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T12:13:13Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ebb8c88da31e400c93d2d55f5c587c2d2022-12-22T00:24:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013843810.1371/journal.pone.0138438Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight.Mohd RehanEjaz AhmadIshfaq A SheikhAdel M AbuzenadahGhazi A DamanhouriOsama S BajouhSamera F AlBasriMansour M AssiriMohd A BegExposure to toxic industrial chemicals that have capacity to disrupt the endocrine system, also known as endocrine disrupting chemicals (EDCs), has been increasingly associated with reproductive problems in human population. Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) and 4-tert-octylphenol (OP; 4-(1,1,3,3-tetramethylbutyl)phenol) are among the most common environmental contaminants possessing endocrine disruption properties and are present in plastics, epoxy resins, detergents and other commercial products of common personal and industrial use. A metabolite of BPA, 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is about 1000 times more biologically active compared to BPA. Epidemiological, clinical, and experimental studies have shown association of BPA and OP with adverse effects on male and female reproductive system in human and animals. The endocrine disruption activity can occur through multiple pathways including binding to steroid receptors. Androgen receptor (AR) and progesterone receptor (PR) are critical for reproductive tract growth and function. Structural binding characterization of BPA, MBP, and OP with AR and PR using molecular docking simulation approaches revealed novel interactions of BPA with PR, and MBP and OP with AR and PR. For BPA, MBP, and OP, five AR interacting residues Leu-701, Leu-704, Asn-705, Met-742, and Phe-764 overlapped with those of native AR ligand testosterone, and four PR interacting residues Leu-715, Leu-718, Met-756, and Met-759 overlapped with those of PR co-complex ligand, norethindrone. For both the receptors the binding strength of MBP was maximum among the three compounds. Thus, these compounds have the potential to block or interfere in the binding of the endogenous native AR and PR ligands and, hence, resulting in dysfunction. The knowledge of the key interactions and the important amino-acid residues also allows better prediction of potential of xenobiotic molecules for disrupting AR- and PR-mediated pathways, thus, helping in design of less potent alternatives for commercial use.http://europepmc.org/articles/PMC4574962?pdf=render |
| spellingShingle | Mohd Rehan Ejaz Ahmad Ishfaq A Sheikh Adel M Abuzenadah Ghazi A Damanhouri Osama S Bajouh Samera F AlBasri Mansour M Assiri Mohd A Beg Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight. PLoS ONE |
| title | Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight. |
| title_full | Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight. |
| title_fullStr | Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight. |
| title_full_unstemmed | Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight. |
| title_short | Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl-2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert-Octylphenol: A Computational Insight. |
| title_sort | androgen and progesterone receptors are targets for bisphenol a bpa 4 methyl 2 4 bis p hydroxyphenyl pent 1 ene a potent metabolite of bpa and 4 tert octylphenol a computational insight |
| url | http://europepmc.org/articles/PMC4574962?pdf=render |
| work_keys_str_mv | AT mohdrehan androgenandprogesteronereceptorsaretargetsforbisphenolabpa4methyl24bisphydroxyphenylpent1eneapotentmetaboliteofbpaand4tertoctylphenolacomputationalinsight AT ejazahmad androgenandprogesteronereceptorsaretargetsforbisphenolabpa4methyl24bisphydroxyphenylpent1eneapotentmetaboliteofbpaand4tertoctylphenolacomputationalinsight AT ishfaqasheikh androgenandprogesteronereceptorsaretargetsforbisphenolabpa4methyl24bisphydroxyphenylpent1eneapotentmetaboliteofbpaand4tertoctylphenolacomputationalinsight AT adelmabuzenadah androgenandprogesteronereceptorsaretargetsforbisphenolabpa4methyl24bisphydroxyphenylpent1eneapotentmetaboliteofbpaand4tertoctylphenolacomputationalinsight AT ghaziadamanhouri androgenandprogesteronereceptorsaretargetsforbisphenolabpa4methyl24bisphydroxyphenylpent1eneapotentmetaboliteofbpaand4tertoctylphenolacomputationalinsight AT osamasbajouh androgenandprogesteronereceptorsaretargetsforbisphenolabpa4methyl24bisphydroxyphenylpent1eneapotentmetaboliteofbpaand4tertoctylphenolacomputationalinsight AT samerafalbasri androgenandprogesteronereceptorsaretargetsforbisphenolabpa4methyl24bisphydroxyphenylpent1eneapotentmetaboliteofbpaand4tertoctylphenolacomputationalinsight AT mansourmassiri androgenandprogesteronereceptorsaretargetsforbisphenolabpa4methyl24bisphydroxyphenylpent1eneapotentmetaboliteofbpaand4tertoctylphenolacomputationalinsight AT mohdabeg androgenandprogesteronereceptorsaretargetsforbisphenolabpa4methyl24bisphydroxyphenylpent1eneapotentmetaboliteofbpaand4tertoctylphenolacomputationalinsight |