Binding Study of Cis-Atovaquone with Cytochrome bc1 of Yeast

Srijita Basumallick; T. N. Guru Row

doi:10.4236/cmb.2015.54007

Home > Journals > Biomedical & Life Sciences > CMB

Computational Molecular Bioscience > Vol.5 No.4, December 2015

Binding Study of Cis-Atovaquone with Cytochrome bc1 of Yeast ()

Srijita Basumallick^1,2, T. N. Guru Row¹

¹Solid State Chemistry and Structural Unit, Indian Institute of Science, Bangalore, India.
²Department of Chemistry, National Institute of Technology, Agartala, India.

DOI: 10.4236/cmb.2015.54007 PDF HTML XML 2,373 Downloads 2,882 Views

Abstract

Tans-Atovaquone is widely used as an effective drug to treat uncomplicated malaria. But its cis-isomer is not a drug. In the present study, we report energy minimized binding pattern of trans-Atovaquone and its cisisomer with cytochrome bc1 (cytbc1) of yeast. The new feature of this molecular docking computation is that structural parameters of the drug molecules have been determined from their crystal structures. The energy minimized structures of protein-drug complexes show that H-bond distant between His-181 of cytochrome bc1 and C=O of Atovaquone for trans-Atovaquone is 2.85 Å and 5.3 Å with the cis-isomer. The role of this H-bonding interaction in dictating drug potency is in conformity with proton-coupled electron transport mechanism of drug action.

Keywords

Anti-Malarial Drug, Crystal Structures, Atovaquone, Docking-Studies

Share and Cite:

Basumallick, S. and Row, T. (2015) Binding Study of Cis-Atovaquone with Cytochrome bc1 of Yeast. Computational Molecular Bioscience, 5, 57-63. doi: 10.4236/cmb.2015.54007.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	WHO World Malaria Report 2014. http://www.who.int/malaria/media/world_malaria_report_2014/en/
[2]	Tuteja, R. (2007) Malaria—An Overview. FEBS Journal, 274, 4670-4679. http://dx.doi.org/10.1111/j.1742-4658.2007.05997.x
[3]	Wongsrichanalai, C., Pickard, A.L., Wernsdorfer, W.H. and Meshnick, S.R. (2002) Epidemiology of Drug-Resistant Malaria. The Lancet Infectious Diseases, 2, 209-218. http://dx.doi.org/10.1016/S1473-3099(02)00239-6
[4]	Joy, D., Feng, X., Mu, J., Furuya, T., Chotivanich, K., Krettl, A.U., Ho, M., Wang, A., White, N.J., Suh, E., Beerli, P. and Su, X. (2003) Early Origin and Recent Expansion of Plasmodium falciparum. Science, 300, 318-321. http://dx.doi.org/10.1126/science.1081449
[5]	Dorn, A., Vippagunta, S.R., Matile, H., Jaquet, C., Vennerstrom, J.L. and Ridley, R.G. (1998) An Assessment of Drug-Haematin Binding as a Mechanism for Inhibition of Haematin Polymerisation by Quinoline Antimalarials. Biochemical Pharmacology, 55, 727-736. http://dx.doi.org/10.1016/S0006-2952(97)00510-8
[6]	Banerjee, R., Liu, J., Beatty, W., Pelosof, L., Klemba, M. and Goldberg, D.E. (2002) Four Plasmepsins Are Active in the Plasmodium falciparum Food Vacuole, Including a Protease with an Active-Site Histidine. Proceedings of the National Academy of Sciences of the United States of America, 99, 990-995. http://dx.doi.org/10.1073/pnas.022630099
[7]	Egan, T.J., Ross, D.C. and Adams, P.A. (1994) Quinoline Anti-Malarial Drugs Inhibit Spontaneous Formation of β-Haematin (Malaria Pigment). FEBS Letters, 352, 54-57. http://dx.doi.org/10.1016/0014-5793(94)00921-X
[8]	Slater, A.F.G. and Cerami, A. (1992) Inhibition by Chloroquine of a Novel Haem Polymerase Enzyme Activity in Malaria Trophozoites. Nature, 355, 167-169. http://dx.doi.org/10.1038/355167a0
[9]	Pandey, A.V., Babbarwal, V.K., Okoyeh, J.N., Joshi, R.M., Puri, S.K., Singh, R.L. and Chauhan, V.S. (2003) Hemozoin Formation in Malaria: A Two-Step Process Involving Histidine-Rich Proteins and Lipids. BBRC, 308, 736-743. http://dx.doi.org/10.1016/S0006-291X(03)01465-7
[10]	Meshnick, S.R. (2002) Artemisinin: Mechanisms of Action, Resistance and Toxicity. International Journal for Parasitology, 13, 1655-1660. http://dx.doi.org/10.1016/S0020-7519(02)00194-7
[11]	Mongan, P.D., Capacchione, J., Karaian, J., Dubois, D., Keneally, R. and Sharma, P. (2002) Pyruvate Improves Redox Status and Decreases Indicators of Hepatic Apoptosis during Hemorrhagic Shock in Swine. American Journal of Physiology-Heart and Circulatory Physiology, 283, 1634-1644. http://dx.doi.org/10.1152/ajpheart.01073.2001
[12]	Basset, G.J.C., Quinlivan, E.P., Gregory, J.F. and Hanson, A.D. (2005) Folate Synthesis and Metabolism in Plants and Prospects for Biofortification. Crop Science, 45, 449-453. http://dx.doi.org/10.2135/cropsci2005.0449
[13]	Myllykallio, H., Leduc, D., Filee, J. and Liebl, U. (2003) Life without Dihydrofolate Reductase FolA. Trends in Microbiology, 11, 220-223. http://dx.doi.org/10.1016/S0966-842X(03)00101-X
[14]	Ridley, R.G. (2002) Medical Need, Scientific Opportunity and the Drive for Antimalarial Drugs. Nature, 415, 686-693. http://dx.doi.org/10.1038/415686a
[15]	Fontaine, E., Ichas, F.O. and Bernardi, P.A. (1998) Ubiquinone-Binding Site Regulates the Mitochondrial Permeability Transition Pore. Journal of Biological Chemistry, 273, 25734-25740. http://dx.doi.org/10.1074/jbc.273.40.25734
[16]	Tielens, A.G.M. and Hellemond, J.J.V. (1998) The Electron Transport Chain in Anaerobically Functioning Eukaryotes. BBA Bioenergetics, 1365, 71-78. http://dx.doi.org/10.1016/S0005-2728(98)00045-0
[17]	Kroger, A. and Gwith, M.K. (1973) The Kinetics of the Redox Reactions of Ubiquinone Related to the Electron-Transport Activity in the Respiratory Chain. European Journal of Biochemistry, 34, 358-368. http://dx.doi.org/10.1111/j.1432-1033.1973.tb02767.x
[18]	Hunte, C., Birth, D. and Kao, W.C. (2014) Structural Analysis of Atovaquone Inhibited Cytochrome bc1 Complex Revels the Molecular Basis of Antimalarial Drug Action. Nature Communication, 5029, 1-11. http://dx.doi.org/10.1038/ncomms5029
[19]	Kessl, J.J., Lange, B.B., Merbitz, Z.T., Zwicker, K., Hill, P., Meunier, B., Hildur, P., lsdo, T., Hunte, C., Meshnick, S. and Trumpower, B.L. (2003) Molecular Basis for Atovaquone Binding to the Cytochrome bc1 Complex. Journal of Biological Chemistry, 278, 31312-31318. http://dx.doi.org/10.1074/jbc.M304042200
[20]	Zhang, Z., Huang, L., Shulmeister, V.M., Chi, Y., Kim, K.K., Hung, L., Croftsk, A.R., Berry, E.A. and Kim, S. (1998) Electron Transfer by Domain Movement in Cytochrome bc1. Nature, 392, 677-684. http://dx.doi.org/10.1038/33612
[21]	Nayek, S.K., Basumallick, S., Kanaujia, S.P., Sekhar, K., Ranganathan, K.R., Ananthalakshmi, V., Jeyaraman, G., Saralaya, S., Nagarajan, K. and Guru Row, T.N. (2013) Crystal Structures and Binding Studies of Atovaquone and Its Derivatives with Cytochrome bc1: A Molecular Basis for Drug Design. Crystal Engineering Communication, 15, 4871-4884.
[22]	Kirkpatrick, S., Gelatt, C.D. and Vecchi, M.P. (1983) Optimization by Simulated Annealing. Science, 220, 671-680. http://dx.doi.org/10.1126/science.220.4598.671
[23]	Metropolis, N. and Ulam, S. (1949) The Monte Carlo Method. Journal of the American Statistical Association, 44, 335-341. http://dx.doi.org/10.1080/01621459.1949.10483310
[24]	Meng, E.C., Shoichet, B.K. and Kuntz, I.D. (1992) Automated Docking with Grid-Based Energy Evaluation. Journal of Computational Chemistry, 13, 505-524. http://dx.doi.org/10.1002/jcc.540130412
[25]	Solis, F.J. and Wets, R.J.B. (1981) Minimization by Random Search Techniques. Mathematics of Operations Research, 6, 19-30. http://dx.doi.org/10.1287/moor.6.1.19
[26]	Boschitsch, A.H. and Fenley, M.O. (2004) Hybrid Boundary Element and Finite Difference Method for Solving the Nonlinear Poisson—Boltzmann Equation. Journal of Computational Chemistry, 25, 935-955. http://dx.doi.org/10.1002/jcc.20000
[27]	Morris, G.M., Goodsell, D.S., Huey, R., Hart, W.E., Halliday, R.S., Belew, R.K. and Olson, A.J. (2001) Autodock Version 3.0.5. Scripps Research Institute, San Diego.
[28]	Barragan, A.M., Crofts, A.R., Schulten, K and Solovyov, I.A. (2015) Identification of Ubiquinol Binding Motifs at the Q0—Site of the Cytochrome bc1 Complex. Journal of Physical Chemistry B, 119, 433-447. http://dx.doi.org/10.1021/jp510022w