Conservation of dinitroani-line/phosphorothioamidate site of α-tubulin in Plasmodium species distributed in India

  • P. A. Karpov
  • O. M. Demchuk
  • S. P. Ozheredov
  • S. I. Spivak
  • A. I. Yemets
  • Ya. B. Blume
DOI: https://doi.org/10.7124/FEEO.v24.1124

Abstract

Aim. To evaluate polymorphism of dinitroaniline/phosphorothioamidate binding site in α-tubulin molecules from Plasmodium species (P. falciparum, P. vivax, P. ovale, and P. malariae) and strains discovered in India. Methods. Literature and database search. Bioinformatical comparison of protein sequences and structures. Multiple sequence alignment, phylogenetic profiling, protein structure modeling, etc. Results. 14 complete sequences of α-tubulin from four Plasmodium species were selected from UniProtKB. Despite certain differences in complete sequences of α-tubulin molecules from different Plasmodium species and strains, sites of their interaction with dinitroaniline and phosphorothioamidate compounds were shown to be identical. Conclusions. Complete identity of dinitroaniline/phosphorothioamidate binding sites in all studied isotypes of α-tubulin molecules from P. falciparum, P. vivax, P. ovale, and P. malariae was confirmed. This suggests identity of the ligand-protein interaction mechanism and similar destabilizing effect of dinitroaniline and phosphorothioamidate compounds on microtubules of all Plasmodium species officially registered in India.

Keywords: malaria, Plasmodium, α-tubulin, dinitroanilines, phosphorothioamidates, binding site.

References

Schantz-Dunn J., Nour N.M. Malaria and pregnancy: a global health perspective. Rev. Obstet. Gynecol. 2009. Vol. 2 (3). P. 186–192.

Molina-Cruz A., DeJong R.J., Ortega C., Haile A., Abban E., Rodrigues J., Jaramillo-Gutierrez G., Barillas-Mury C. Some strains of Plasmodium falciparum, a human malaria parasite, evade the complement–like system of Anopheles gambiae mosquitoes. Proc. Natl. Acad. Sci. USA. 2012. Vol. 109 (28). E1957–1962.

Das A., Anvikar A.R., Cator L.J., Dhiman R.C., Eapen A., Mishra N., Nagpal B.N., Nanda N., Raghavendra K., Read A.F., Sharma S.K., Singh O.P., Singh V., Sinnis P., Srivastava H.C., Sullivan S.A., Sutton P.L., Thomas M.B., Carlton J.M., Vale-cha N. Malaria in India: The center for the study of complex malaria in India. Acta Tropica. 2012. Vol. 121 (3). P. 267–273.

Anvikar A.R., Shah N., Dhariwal A.C., Sonal G.S., Pradhan M.M., Ghosh S.K., Valecha N. Epidemiology of Plasmodium vivax malaria in India. Am. J. Trop. Med. Hyg. 2016. Vol. 95 (6S). P. 108–120.

Sharma S.K., Tyagi P.K., Padhan K., Upadhyay A.K., Haque M.A., Nanda N., Joshi H., Biswas S., Adak T., Das B.S., Chau-han V.S., Chitnis C.E., Subbarao S.K. Epidemiology of malaria transmission in forest and plain ecotype villages in Sundargarh District, Orissa, India. Trans. R. Soc. Trop. Med. Hyg. 2006. Vol. 100 (10). P. 917–925.

Britsun V.M., Yemets А.І., Lozinskii M.О., Blume Ya.B. 2,6–Dinitroanilines: synthesis, herbicidal and antiprotozoan proper-ties. Ukr. Bioorg. Acta. 2009. Vol. 7 (1). P. 16–27.

Ota S., Tomioka S., Sogawa H., Satou R., Fujimori M., Karpov P., Shulga S., Blume Ya., Kurita N. Binding properties be-tween curcumin and malarial tubulin: molecular–docking and ab initio fragment molecular orbital calculations. Chem-Bio In-formatics J. 2018. Vol. 18. P. 44–57.

Usanga E.A., O’Brien E., Luzzato L. Mitotic inhibitors arrest the growth of Plasmodium falciaprum. FEBS Lett. 1986. Vol. 209. P. 23–27.

Bell A., Wernli B., Franklin R.M. Effects of microtubule inhibitors on protein synthesis in Plasmodium falciparum. Parasitol. Res. 1993. Vol. 79. P. 146–152.

Dieckmann-Schuppert A., Franklin R.M. Compounds binding to cytoskeletal proteins are active against Plasmodium falciparum in vitro. Cell Biol. Int. 1989. Vol. 13. P. 411–418.

Nath J., Schneider I. Anti-malarial effects of the anti-tubulin herbicide trifluralin: studies in Plasmodium falciparum. Clin. Res. 1992. Vol. 40. #331A.

Fennell B.J., Carolan S., Pettit G.R., Bell A. Effects of the antimitotic natural product dolastatin 10, and related peptides, on the human malarial parasite Plasmodium falciparum. J. Antimicrob. Chemother. 2003. Vol. 51. P. 833–841.

Schrevel J., Sinou V., Grellier P., Frappier F., Guйnard D., Potier P. Interactions between docetaxel (Taxotere) and Plasmodium falciparum – infected erythrocytes. Proc. Natl. Acad. Sci. USA. 1994. Vol. 91. P. 8472–8476.

Pouvelle B., Farley P.J., Long C.A., Taraschi T.F. Taxol arrests the development of blood-stage Plasmodium falciparum in vitro and Plasmodium chabaudi adami in malaria-infected mice. J. Clin. Invest. 1994. Vol. 94. P. 413–417.

Bell A. Microtubule inhibitors as potential antimalarial agents. Parasitol. Today. 1998. Vol. 14. P. 234–240.

Fennell B.J., Naughton J.A., Dempsey E., Bell A. Cellular and molecular actions of dinitroaniline and phosphorothioamidate herbicides on Plasmodium falciparum: tubulin as a specific antimalarial target. Mol. Biochem. Parasitol. 2006. Vol. 145 (2). P. 226–238.

Corral M.G., Leroux J., Stubbs K.A., Mylne J.S. Herbicidal properties of antimalarial drugs. Sci. Repts. 2017. Vol. 7. # 45871.

Lyons–Abbott S., Sackett D.L., Wloga D., Gaertig J., Morgan R.E., Werbovetz K.A., Morrissette N.S. б–Tubulin mutations alter oryzalin affinity and microtubule assembly properties to confer dinitroaniline resistance. Eukar. Cell. 2010. Vol. 9 (12). P. 1825–1834.

Yemets A.I., Blume Y.B. Antimitotic drugs for microprotoplast–mediated chromosome transfer in plant genomics, cell engineering and breeding. In: Blume Y.B., Baird W.V., Yemets A.I., Breviario D. (eds) The Plant Cytoskeleton: a Key Tool for Agro-Biotechnology. Springer, Dordrecht, 2008. P. 419–434.

Morrissette N.S., Mitra A., Sept D., Sibley L.D. Dinitroanilines bind α-tubulin to disrupt microtubules. Mol. Biol. Cell. 2004. Vol. 15 (4). P. 1960–1968.

Morgan R.E., Ahn S., Nzimiro S., Fotie J., Phelps M.A., Cotrill J., Yakovich A.J., Sackett D.L., Dalton J.T., Werbovetz K.A. Inhibitors of tubulin assembly identified through screening a compound library. Chem. Biol. Drug Design. 2008. Vol. 72 (6). P. 513–524.

Robinson D.R., Sherwin T., Ploubidou A., Byard E.H., Gull K. Microtubule polarity and dynamics in the control of organelle positioning, segregation, and cytokinesis in the trypanosome cell cycle. J. Cell Biol. 1995. Vol. 128. P. 1163–1172.

Werbovetz K.A. Tubulin as an antiprotozoal drug target. Mini Rev. Med. Chem. 2002. Vol. 2. P. 519–529.

Dhooghe E., Van L.K., Eeckhaut T., Leus L., Van H.J. Mitotic chromosome doubling of plant tissues in vitro. Plant Cell Tiss. Org. Cult. 2011. Vol. 104. P. 359–373.

UniProt Consortium T. UniProt: the universal protein knowledgebase. Nucl. Acids Res. 2018. Vol. 46 (5). P. 2699.

Nyporko A.Yu., Yemets A.I., Klimkina L.A., Blume Ya.B. Sensitivity of Eleusine indica callus to trifluralin and amiprophos-methyl in correlation with the binding of these compounds to tubulin. Russ. J. Plant Physiol. 2002. Vol. 49 (3). P. 413–418.

Nyporko A.Y., Yemets A.I., Brytsun V.N., Lozinsky M.O., Blume Y.B. Structural and biological characterization of the tubu-lin interaction with dinitroanilines. Cytol. Genet. 2009. Vol. 43. P. 267–282.

Chu Z., Chen J., Nyporko A., Han H., Yu Q., Powles S. Novel α-tubulin mutations conferring resistance to dinitroaniline herbicides in Lolium rigidum. Front. Plant Sci. 2018. Vol. 9. P. 97. doi.org/10.3389/fpls.2018.00097.

Ma C., Li C., Ganesan L., Oak J., Tsai S., Sept D., Morrissette N.S. Mutations in alpha–tubulin confer dinitroaniline resistance at a cost to microtubule function. Mol. Biol. Cell. 2007. Vol. 18 (12). P. 4711–4720.

Ma C., Tran J., Gu F., Ochoa R., Li C., Sept D., Werbovetz K., Morrissette N. Dinitroaniline activity in Toxoplasma gondii expressing wild–type or mutant alpha–tubulin. Antimicrob. Agents Chemother. 2010. Vol. 54 (4). P. 1453–1460.

Waterhouse A., Bertoni M., Bienert S., Studer G., Tauriello G., Gumienny R., Heer F.T., de Beer T.A.P., Rempfer C., Bordoli L., Lepore R., Schwede T. SWISS–MODEL: homology modelling of protein structures and complexes. Nucl. Acids Res. 2018. Vol. 46 (W1). W296–W303.

Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissig H., Shindyalov I.N., Bourne P.E. The Protein Data Bank. Nucl. Acids Res. 2000. Vol. 28 (1). P. 235–242.

Ichikawa M., Liu D., Kastritis P.L., Basu K., Hsu T.C., Yang S., Bui K.H. Subnanometre–resolution structure of the doublet microtubule reveals new classes of microtubule–associated proteins. Nat. Commun. 2017. Vol. 8. P. 15035. doi: 10.1038/ncomms15035.

Leverett C.A., Sukuru S.C., Vetelino B.C., Musto S., Parris K., Pandit J., Loganzo F., Varghese A.H., Bai G., Liu B., Liu D., Hudson S., Doppalapudi V.R., Stock J., O'Donnell C.J., Subramanyam C. Design, synthesis, and cytotoxic evaluation of novel tubulysin analogues as ADC payloads. ACS Med. Chem. Lett. 2016. Vol. 7. P. 999–1004.

Larkin M.A., Blackshields G., Brown N.P., Chenna R., McGettigan P.A., McWilliam H., Valentin F., Wallace I.M., Wilm A., Lopez R., Thompson J.D., Gibson T.J., Higgins D.G. ClustalW and ClustalX version 2.0. Bioinformatics. 2007. Vol. 23 (21). P. 2947–2948.

Kumar S., Stecher G., Tamura K. MEGA7: Molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol. Biol. Evol. 2016. Vol. 33 (7). P. 1870–1874.

Nogales E., Wolf S.G., Downing K.H. Structure of the alpha beta tubulin dimer by electron crystallography. Nature. 1998. Vol. 391 (6663). P. 199–203.

Blume Ya.B., Nyporko A.Yu., Yemets A.I., Baird W.V. Structural modeling of the interaction of plant α-tubulin with dini-troaniline and phosphoroamidate herbicides. Cell Biol. Int. 2003. Vol. 27 (3). P. 171–174.

Tuszynski J.A., Carpenter E.J., Huzil J.T., Malinski W., Luchko T., Luduena R.F. The evolution of the structure of tubulin and its potential consequences for the role and function of microtubules in cells and embryos. Int. J. Dev. Biol. 2006. Vol. 50 (2–3). P. 341–358.