Evaluation Of Theileria Parva Enolase As A Target For Designing New Generation Antiheilerial Drug

Evaluation Of Theileria Parva Enolase As A Target For Designing New Generation Antiheilerial Drug

Enolase (2-phospho-D-glycerate hydrolase) enzyme has been characterized extensively and approved as a molecular drug target for rational drug discovery in apicomplexans such as plasmodium sp., toxoplasma gondii  but not in the Theileria parva which causative agent of  East Coast Fever(ECF) engender serious economic losses.  For the aim of identifying a key drug target, we have analyzed Theileria parva’s enolase sequence and we have constructed three-dimensional (3D) structure of that enolase and mammalian host Bos taurus  enolase(BtEno). Constructed model was approved, structurally analyzed and conceivable ligand binding pockets were identified for the first time in the literature. In this study, we reported significant findings, a penta-peptide and three different dipeptide insertions in TpENO (D103W104G105Y106C107, T147D148, K261E262, K317L318), when compare the sequences of enolase gene with its counterpart host BtEno. The homology modeling revealed that these insertions constituted loops that absent in B. taurus enolase seem to be important lead structures which can be used as binding sites for inhibition of TpEno.  

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  • Bhattacharya, D., & Cheng, J., 2013. 3Drefine: consistent protein structure refinement by optimizing hydrogen bonding network and atomic-level energy minimization. Proteins, 81, 119-131.
  • Bishop, R., Geysen, D., Spooner, P., Skilton, R., Nene, V., Dolan, T., & Morzaria, S. , 2001. Molecular and immunological characterisation of Theileria parva stocks which are components of the 'Muguga cocktail' used for vaccination against East Coast fever in cattle. Vet Parasitol, 94, 227-237.
  • Cameron, A., Read, J., Tranter, R., Winter, V. J., Sessions, R. B., Brady, R. L., Vivas, L., Easton, A., Kendrick, H., Croft, S. L., Barros, D., Lavandera, J. L., Martin, J. J., Risco, F., Garcia-Ochoa, S., Gamo, F. J., Sanz, L., Leon, L., Ruiz, J. R., Gabarro, R., Mallo, A., & Gomez de las Heras, F. , 2004. Identification and activity of a series of azole-based compounds with lactate dehydrogenase-directed anti-malarial activity. J Biol Chem, 279, 31429-31439.
  • Certa, U., Ghersa, P., Dobeli, H., Matile, H., Kocher, H. P., Shrivastava, I. K., Shaw, A. R., & Perrin, L. H. , 1988). Aldolase activity of a Plasmodium falciparum protein with protective properties. Science, 240, 1036-1038
  • Chenna, R., Sugawara, H., Koike, T., Lopez, R., Gibson, T. J., Higgins, D. G., & Thompson, J. D. , 2003. Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res, 31, 3497-3500.
  • Colovos, C., & Yeates, T. O. , 1993. Verification of protein structures: patterns of nonbonded atomic interactions. Protein Sci, 2, 1511-1519.
  • Dolan, T. T., Injairu, R., Gisemba, F., Maina, J. N., Mbadi, G., Mbwiria, S. K., Mulela, G. H., & Othieno, D. A., 1992. A clinical trial of buparvaquone in the treatment of East Coast fever. Vet Rec, 130, 536-538.
  • Dunn, C. R., Banfield, M. J., Barker, J. J., Higham, C. W., Moreton, K. M., Turgut-Balik, D., Brady, R. L., & Holbrook, J. J. , 1996. The structure of lactate dehydrogenase from Plasmodium falciparum reveals a new target for anti-malarial design. Nature Structural Biology, 3, 912-915.
  • Foth, B. J., Stimmler, L. M., Handman, E., Crabb, B. S., Hodder, A. N., & McFadden, G. I. , 2005. The malaria parasite Plasmodium falciparum has only one pyruvate dehydrogenase complex, which is located in the apicoplast. Molecular Microbiology, 55, 39-53.
  • Gardner, M. J., Bishop, R., Shah, T., de Villiers, E. P., Carlton, J. M., Hall, N., Ren, Q., Paulsen, I. T., Pain, A., Berriman, M., Wilson, R. J., Sato, S., Ralph, S. A., Mann, D. J., Xiong, Z., Shallom, S. J., Weidman, J., Jiang, L., Lynn, J., Weaver, B., Shoaibi, A., Domingo, A. R., Wasawo, D., Crabtree, J., Wortman, J. R., Haas, B., Angiuoli, S. V., Creasy, T. H., Lu, C., Suh, B., Silva, J. C., Utterback, T. R., Feldblyum, T. V., Pertea, M., Allen, J., Nierman, W. C., Taracha, E. L., Salzberg, S. L., White, O. R., Fitzhugh, H. A., Morzaria, S., Venter, J. C., Fraser, C. M., & Nene, V., 2005. Genome sequence of Theileria parva, a bovine pathogen that transforms lymphocytes. Science, 309, 134-137.
  • Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel RD, Bairoch A., Gardner, M. J., Bishop, R., Shah, T., de Villiers, E. P., Carlton, J. M., Hall, N., Ren, Q., Paulsen, I. T., Pain, A., Berriman, M., Wilson, R. J., Sato, S., Ralph, S. A., Mann, D. J., Xiong, Z., Shallom, S. J., Weidman, J., Jiang, L., Lynn, J., Weaver, B., Shoaibi, A., Domingo, A. R., Wasawo, D., Crabtree, J., Wortman, J. R., Haas, B., Angiuoli, S. V., Creasy, T. H., Lu, C., Suh, B., Silva, J. C., Utterback, T. R., Feldblyum, T. V., Pertea, M., Allen, J., Nierman, W. C., Taracha, E. L., Salzberg, S. L., White, O. R., Fitzhugh, H. A., Morzaria, S., Venter, J. C., Fraser, C. M., & Nene, V. (2005). Genome sequence of Theileria parva, a bovine pathogen that transforms lymphocytes. Science, 309(5731), 134-1372003 ExPASy: The proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res.31, 3784-8.
  • Geourjon C, Deleage G., 1995. SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Comput Appl Biosci. 11, 681-4.
  • Guo, A. Y., Zhu, Q. H., Chen, X., & Luo, J. C., 2007. [GSDS: a gene structure display server]. Yi Chuan, 29, 1023-1026.
  • Hayashida, K., Abe, T., Weir, W., Nakao, R., Ito, K., Kajino, K., Suzuki, Y., Jongejan, F., Geysen, D., & Sugimoto, C. , 2013. Whole-genome sequencing of Theileria parva strains provides insight into parasite migration and diversification in the African continent. DNA Res, 20, 209-220.
  • Huang, B. , 2009. MetaPocket: a meta approach to improve protein ligand binding site prediction. Omıcs. 13, 325- 30. doi: 10.1089/omi.2009.0045.
  • Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N., & Sternberg, M. J. , 2015. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc, 10, 845-858.
  • Kumpula, E. P., & Kursula, I. , 2015. Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies? Acta Crystallographica Section F-Structural Biology Communications, 71, 500-513.
  • Labbe, M., Peroval, M., Bourdieu, C., Girard-Misguich, F., & Pery, P. , 2006. Eimeria tenella enolase and pyruvate kinase: a likely role in glycolysis and in others functions. Int J Parasitol, 36, 1443-1452.
  • Lau, A. O. , 2009. An overview of the Babesia, Plasmodium and Theileria genomes: a comparative perspective. Mol Biochem Parasitol, 164, 1-8.
  • Lovell, S. C., Davis, I. W., Arendall, W. B., 3rd, de Bakker, P. I., Word, J. M., Prisant, M. G., Richardson, J. S., & Richardson, D. C. ,2003. Structure validation by Calpha geometry: phi,psi and Cbeta deviation. Proteins, 50, 437-450.
  • Maithal, K., Ravindra, G., Balaram, H., & Balaram, P. , 2002. Inhibition of plasmodium falciparum triose-phosphate isomerase by chemical modification of an interface cysteine. Electrospray ionization mass spectrometric analysis of differential cysteine reactivities. J Biol Chem, 277, 25106-25114.
  • McHardy, N., Wekesa, L. S., Hudson, A. T., & Randall, A. W., 1985. Antitheilerial activity of BW720C (buparvaquone): a comparison with parvaquone. Res Vet Sci, 39, 29-33.
  • Mhadhbi, M., Chaouch, M., Ajroud, K., Darghouth, M. A., & BenAbderrazak, S. , 2015. Sequence Polymorphism of Cytochrome b Gene in Theileria annulata Tunisian Isolates and Its Association with Buparvaquone Treatment Failure. PLoS One, 10, e0129678.
  • Mhadhbi, M., Naouach, A., Boumiza, A., Chaabani, M. F., BenAbderazzak, S., & Darghouth, M. A. , 2010. In vivo evidence for the resistance of Theileria annulata to buparvaquone. Vet Parasitol, 169, 241-247.
  • Olwoch, J. M., Reyers, B., Engelbrecht, F. A., & Erasmus, B. F. N. , 2008. Climate change and the tick-borne disease, Theileriosis (East Coast fever) in sub-Saharan Africa. Journal of Arid Environments, 72, 108-120.
  • Oura, C. A., Bishop, R., Wampande, E. M., Lubega, G. W., & Tait, A. , 2004. The persistence of component Theileria parva stocks in cattle immunized with the 'Muguga cocktail' live vaccine against East Coast fever in Uganda. Parasitology, 129, 27-42.
  • Pal-Bhowmick, I., Sadagopan, K., Vora, H. K., Sehgal, A., Sharma, S., & Jarori, G. K. , 2004. Cloning, over-expression, purification and characterization of Plasmodium falciparum enolase. Eur J Biochem, 271, 4845-4854.
  • Piper, R., Lebras, J., Wentworth, L., Hunt-Cooke, A., Houze, S., Chiodini, P., & Makler, M. , 1999. Immunocapture diagnostic assays for malaria using Plasmodium lactate dehydrogenase (pLDH). Am J Trop Med Hyg, 60, 109-118.
  • Sharifiyazdi, H., Namazi, F., Oryan, A., Shahriari, R., & Razavi, M. , 2012. Point mutations in the Theileria annulata cytochrome b gene is associated with buparvaquone treatment failure. Vet Parasitol, 187, 431-435.
  • Singh, D. K., Thakur, M., Raghav, P. R., & Varshney, B. C. , 1993. Chemotherapeutic trials with four drugs in crossbred calves experimentally infected with Theileria annulata. Res Vet Sci, 54, 68-71.
  • Walker, A. R. , 2007. Theileriosis and the tick control conundrum: a better way forward? Vet J, 173, 248-249.
  • Wiederstein, M., & Sippl, M. J. , 2007. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res, 35(Web Server issue), W407-410.