Nonylphenol and bisphenol A binding studies with antioxidant enzymes through homology modeling and molecular docking methods
M. Jayakanthan1#, R. Jubendradass2, Shereen Cynthia D’Cruz2, P. P. Mathur1,2,3*
1 Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Pondicherry- 605 014, India 2 Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry - 605 014, India 3 KIIT University, Bhubaneswar - 751024, India
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500 007, Andhra Pradesh, India
* Corresponding author
E-mail: email@example.com, firstname.lastname@example.org
Key words: Nonylphenol; Bisphenol A; antioxidant; homology modeling; molecular docking
Bisphenol A (BPA) and nonylphenol (NP) are phenolic compounds used widely by the industries. BPA and NP are endocrine disruptors possessing estrogenic properties. Several studies have reported that BPA and NP induce oxidative stress in various organs or cell types in animals, by inhibiting the activities of antioxidant enzymes like catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. However, it is not understood how BPA and NP interact with these enzymes and inhibit their functions. Hence, it would be significant to check, whether binding sites are available for NP and BPA in antioxidant enzymes. In the present study three-dimensional structures of antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase were modeled and docked with BPA and NP. Molecular docking studies revealed that BPA and NP have binding pockets in the antioxidant enzymes. Among the antioxidant enzymes, Catalase was maximally inhibited by BPA and superoxide was maximally inhibited by NP.
Molecular docking is an automated computational technique employed in computer-aided drug design for identification of potent bioactive agents. It operates by identifying the best binding mode of given ligand with its macromolecular target and evaluates the binding affinity, results of which were used in the ranking the best interacting ligands and in selection of promising bioactive compounds. Success of a molecular docking algorithm depends on the implication of efficient search method, which is used for exploring the potential energy landscape of ligands for finding their optimum configuration, accompanied with the proper scoring scheme for evaluating the binding modes of the ligand with their targets. In rigid docking methods, search algorithm employs the rotation and translational functions to locate low energy configurations, while in flexible docking methodology, sampling of various conformations of ligand is performed by altering their torsion angles. Besides, the concept of flexibility is also applied in a method called induced fit docking for searching the possible best interacting conformations of amino acids. Molecular docking is widely used for screening the libraries of compounds, for selection of best interacting hits, and in the design of novel leads based on the available drug molecules (1,2).
In the recent years, there has been much concern regarding the adverse effects of various environmental contaminants on human health. With the advent of industrialization, economic development and urbanization drastic changes occurred in the lifestyle and surroundings of humans, which resulted in the extensive production, and use of substances that could facilitate life. As a result, many potentially hazardous chemicals got released into the environment at an alarming rate and exposure to these chemicals has become inevitable. These chemicals released into the environment turned out to be one of the leading causative factors for the high incidence of various pathological conditions (3,4). Of various...
References: 1. Morris, G.M. and Lim-Wilby, M. (2008) Molecular Docking. In: K. Andreas (Ed.), Molecular Modeling of Proteins (Methods in Molecular Biology), Humana Press, Totowa, New York. pp. 365-382.
2. Brooijmans, N. and Kuntz, I.D. (2003). Molecular recognition and docking algorithms. Annu Rev Biophys Biomol Struct 32, 335–373.
3. Clapp, R.W., Jacobs, M.M., and Loechler, E.L. (2008) Environmental and occupational causes of cancer: new evidence 2005-2007. Rev Environ Health 23, 1–37.
4. Irigaray, P., Newby, J.A., Clapp, R., et al. (2007). Lifestyle-related factors and environmental agents causing cancer: an overview. Biomed Pharmacother 61, 640–658.
5. Vandenberg, L.N., Hauser, R., Marcus, M., et al. (2007) Human exposure to bisphenol A (BPA). Reprod Toxicol 24, 139–177.
6. Howdeshell, K.L., Peterman, P.H., Judy, B.M., et al. (2003) Bisphenol A is released from used polycarbonate animal cages into water at room temperature. Environ Health Perspect 111, 1180–1187.
7. Kang, J.H., Kito, K., and Kondo, F. (2003) Factors influencing the migration of bisphenol A from cans. J Food Prot 66, 1444–1447.
8. Foran, C.M., Bennett, E.R., and Benson, W.H. (2000) Exposure to environmentally relevant concentrations of different nonylphenol formulations in Japanese medaka. Mar Environ Res 50, 135–139.
9. Guenther, K., Heinke, V., Thiele, B., et al. (2002) Endocrine disrupting nonylphenols are ubiquitous in food. Environ Sci Technol 36, 1676–1680.
10. Saito, I., Onuki, A., and Seto, H. (2004) Indoor air pollution by alkylphenols in Tokyo. Indoor Air 14, 325–332.
11. Hanioka, N., Jinno, H., Tanaka-Kagawa, T., et al. (2000) Interaction of bisphenol A with rat hepatic cytochrome P450 enzymes. Chemosphere 41, 973–978.
12. Chitra, K.C. and Mathur, P.P. (2004) Vitamin E prevents nonylphenol -induced oxidative stress in testis of rats. Indian J Exp Biol 42, 220–223.
13. Yasemin, S.K. and Recep, A. (2010) Taurine prevents nonylphenol-induced oxidative stress in rats. J Anim Vet Adv 9, 37–43.
14. Kanner, J., German, J.B., and Kinsella, J.E. (1987) Initiation of lipid peroxidation in biological systems. Crit Rev Food Sci Nutr 25, 317–364.
15. Betteridge, D.J. (2000) What is oxidative stress? Metabolism 49, 3–8.
16. Sies, H. (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82, 291–295.
17. Chitra, K.C., Rao, K.R., and Mathur, P.P. (2003) Effect of bisphenol A and co-admi. nistration of bisphenol A and vitamin C on epididymis of adult rats: a histological and biochemical study. Asian J Androl 5, 203–208
19. Kabuto, H., Amakawa, M., and Shishibori, T. (2004) Exposure to bisphenol A during embryonic/fetal life and infancy increases oxidative injury and causes underdevelopment of the brain and testis in mice. Life Sci 74, 2931–2940.
20. Mao, Z., Zheng, Y.L., and Zhang, Y.Q. (2010) Behavioral impairment and oxidative damage induced by chronic application of nonylphenol. Int J Mol Sci 12, 114–127.
21. Aydogan, M., Korkmaz, A., Barlas, N., et al. (2008) The effect of vitamin C on bisphenol A, nonylphenol and octylphenol induced brain damages of male rats. Toxicology 249, 35–39.
22. Chitra, K.C., Latchoumycandane, C., and Mathur, P.P. (2002) Effect of nonylphenol on the antioxidant system in epididymal sperm of rats. Arch Toxicol 76, 545–551.
23. Laskowski, R.A., MacArthur, M.W., Moss, D.S., et al. (1993) PROCHECK - a program to check the stereochemical quality of protein structures. J App Cryst 26, 283–291.
24. Wiederstein, M. and Sippl, M.J. (2007) ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 35, W407–W410.
26. Hart, P.J., Balbirnie, M.M., Ogihara, N.L., et al. (1999) Nersissian AM, Weiss MS, Valentine JS, Eisenberg D. A structure-based mechanism for copper-zinc superoxide dismutase. Biochemistry 38, 2167–2178.
27. Ko, T.P., Safo, M.K., Musayev, F.N., et al. (2000) Structure of human erythrocyte catalase. Acta Crystallogr D Biol Crystallogr 56, 241–245.
29. Karplus, P.A. and Schulz, G.E. (1989) Substrate binding and catalysis by glutathione reductase as derived from refined enzyme: substrate crystal structures at 2 A resolution. J Mol Biol 210, 163–180.
30. Pai, E.F. and Schulz, G.E. (1983) The catalytic mechanism of glutathione reductase as derived from x-ray diffraction analyses of reaction intermediates. J Biol Chem 258, 1752–1757.
Please join StudyMode to read the full document