International Journal of Bioinformatics and Biomedical Engineering
Articles Information
International Journal of Bioinformatics and Biomedical Engineering, Vol.1, No.2, Sep. 2015, Pub. Date: Aug. 3, 2015
Phylogenetic Relationship Among Apicomlexan Parasites Based on In silico Analysis of Enzymes of the MEP Pathway
Pages: 123-129 Views: 1289 Downloads: 449
[01] Shiv Kumar, Central Drugs Standard Control Organization (East Zone), Ministry of Health and Family Welfare, Government of India, Nizam Palace, Kolkata, India.
[02] Ashish Kumar Gupta, Amity Institute of Biotechnology, Amity University, Sector 125, Uttar Pradesh, India.
[03] Deepak Ganjewala, Amity Institute of Biotechnology, Amity University, Sector 125, Uttar Pradesh, India.
Apicomplexans such as P. falciparum use MEP pathway to synthesize isoprenoids crucial for their survival in the host. Here we report phylogenetic relationship among 11 parasites of phylum apicomplexa based on in silico analysis of enzymes of the MEP pathway with reference to Plasmodium falciparum 3D7. In addition, structure based homology of DXR of apicomlexans were performed with respect to DXR of Mycobacterium tuberculosis in order to gain detail insight of their DXR structure. The study revealed that 9 of 11 apicomlexans showed presence of the MEP pathway and all of its enzymes while the MEP pathway was absent in two members namely Cryptosporidium hominis and C. parvum. In two apicomlexans Toxoplasma gondi and Eimeria tenella an enzyme MCT and in P. knowlesi HDR enzyme of the MEP pathway was absent. Sequence analysis of the MEP pathway enzymes and resultant cladogram indicated that plasmodium sp. can be easily distinguished from non-plasmodium sp. The cladogram revealed close relationship among plasmodium sp. viz., P. falciparum 3D7, P. berghei str. ANKA, P. vivax SaI-1 and P. knowlesi H. Results of structure based homology analysis showed presence of amino acids viz., Thr (T) 21, Gly (G) 22, Ser (S) 23, Ile (I) 24, Gly (G) 47, Gly (G) 48, Ala (A) 49 and Glu (E) 129 in the NADPH binding domain; Asp (D)151, Glu (E)153 and Glu in Mn2+ binding domain and Ser (S)152, Ser (S) 177, His (H) 200, Asn (N) 218 and Lys (K)219 in fosmidomycin binding domain in DXRs of apicomlexans. These amino acids were found to be highly conserved. Thus, MEP pathway enzymes served as excellent tools to discern phylogenetic relationship in apicomlexans and an attractive target for development of new anti-parasitic drugs against these parasitic microorganisms.
Apicomplexa, Apicoplast, Fosmidomycin, Isoprenoid, MEP Pathway, Plasmodium falciparum
[01] Ajioka, J.W., Boothroyd, J.C., Brunk, B.P., Heh, A., Hillier, L., Manger, I.D. et al. (1998). Gene discovery by EST sequencing in Toxoplasma gondii reveals sequences restricted to the Apicomplexa. Genome Research, 8:18-28
[02] Argyrou, A. and Blanchard, J.S. (2004). Kinetic and chemical mechanism of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate isomeroreductase. Biochemistry, 43:4375-4384
[03] Arora, N., Banerjee, A.K. and Murty, U.S.N. (2010). Homology model of 2-C-methyl-D-erythritol 2, 4-cyclodiphosphate (MECP) synthase of Plasmodium falciparum 3D7. Electronic Journal of Biology, 6: 52-57.
[04] Cavalier-Smith, T. (1993). Kingdom protozoa and its 18 phyla. Microbiology Review, 57: 953-994
[05] Cui, L., Fan, Q., Hu, Y., Karamycheva, S.A., Quackenbush, J., Khuntirat, B., Sattabongkot, J. and Carlton, J.M. (2005). Gene discovery in Plasmodium vivax through sequencing of ESTs from mixed blood stages. Molecular and Biochemical Parasitology, 144:1-9
[06] Eisenreich, W., Schwarz, M., Cartayrade, A., Arigoni, D., Zenk, M.H. and Bacher, A. (1998). The deoxyxylulose phosphate pathway of terpenoid biosynthesis in plants and microorganisms. Chemical Biology, 5: R221-R233
[07] Ganjewala, D., Kumar, S. and Luthra, R. (2009). An account of cloned genes of methyl-erythritol-4-phosphate pathway of isoprenoid biosynthesis in plants. Current Issues in Molecular Biology, 11:S35-S45
[08] Gardener, M.J., Hall, N., Funq, E., White, O., Berriman, M., Hyman, R.W., et al (2002). Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, 419:498-511
[09] Goble, J.L., Adendorff, M.R., de Beer, T.A.P., Stephens, L.L and Blatch, G.L. (2010). The malarial drug target Plasmodium falciparum 1-Deoxy-D-Xylulose-5-Phosphate reductoisomerase (PfDXR): Development of a 3-D model for identification of novel, structural and functional features and for inhibitor screening. Protein Peptide Letters, 17:109-120
[10] Henriksson, L.M., Unge, T., Carlsson, J., Aqvist, J., Mowbray, S.L. and Jones TA (2007) Structures of Mycobacterium tuberculosis 1-Deoxy-D-xylulose-5-phosphate reductoisomerase provide new insights into catalysis. Journal of Biological Chemistry, 282:19905-91916
[11] Howe, D.K. (2001). Initiation of a Sarcocystis neurona expressed sequence tag (EST) sequencing project: A preliminary report. Veterinary Parasitology, 95:233-239
[12] Jomaa, H., Wiesner, J., Sanderbrand, S., Altincicek, B., Weidemeyer, C., Hintz, M., Turbachova, I., Ebert, M., Zeidler, J., Lichtenthaler, H.K., Soldatri, D. and Beck, E. (1999). Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science, 285:1573-1576
[13] Kemp, L.E., Bond, C.S. and Hunter, W.N. (2002). Structure of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development. Proceeding of National Academy of Sciences USA, 99: 6591-6596
[14] Lell, B., Ruangweerayut, R., Wiesner, J., Missinou, M.A., Schindler, A., Baranek, T., Hintz, M., Hutchinson, D., Jomaa, H. and Kremsner, P.G. (2003). Fosmidomycin, a novel chemotherapeutic agent for malaria. Antimicrobial Agents Chemotherapy, 47:735-738
[15] Levitt, M. and Perutz, M.F. (1988). Aromatic rings act as hydrogen bond acceptors. Journal of Molecular Biology, 201:751-754
[16] Li, L., Brunk, B.P., Kissinger, J.C., Pape, D., Tang, K., Cole, R.H., et al., (2003). Gene discovery in the apicomplexa as revealed by EST sequencing and assembly of a comparative gene database. Genome Research, 13:443-454
[17] Missinou, M.A., Borrmann, S., Schindler, A., Issifou, S., Adegnika, A.A., Matsiegui, P.B., et al., (2002). Fosmidomycin for malaria. Lancet, 360:1941-1942
[18] Petrullo, L.A., Gallagher, P.J. and Elseviers, D. (1983).The role of 2-methylthio-N6-isopentenyladenosine in readthrough and suppression of nonsense codons in Escherichia coli. Molecular and General Genetics, 190:289-294
[19] Rohdich, F., Eisenreich, W., Wungsintaweekul, J., Hecht, S., Schuhr, C.A. and Bacher, A. (2001). Biosynthesis of terpenoids. 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (IspF) from Plasmodium falciparum. European Journal of Biochemistry, 268:3190-3197
[20] Rohmer, M., Knani, M., Simonin, P., Sutter, B. and Sahm, H. (1993). Isoprenoid biosynthesis in bacteria: a novel pathway for the early steps leading to isopentenyl diphosphate. Biochemical Journal, 295:517-52
[21] Roos, D.S., Crawford, M.J., Donald, R.G., Fraunholz, M., Harb, O.S., He, C.Y., Kissinger, J.C., Shaw, M.K. and Striepen, B. (2002). Mining the Plasmodium genome database to define organellar function: what does the apicoplast do?’, Philosophical Transaction of the Royal Society London B: Biological Science 357:35-46
[22] Steinbacher, S., Kaiser, J., Wungsintaweekul, J., Hecht, S., Eisenreich, W., Gerhardt, S., Bacher, A. and Rohdich, F. (2002). Structure of 2-C-methyl-D-erythritol-2,4-cyclodiphosphate synthase involved in mevalonate independent biosynthesis of isoprenoids. Journal of Molecular Biology, 316:79-88
[23] Takahashi, S., Kuzuyama, T., Watanabe, H. and Seto, H. (1998). A 1-deoxy-D-xyulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative non mevalonate pathway for terpenoid biosynthesis. Proceedings of National Academy of Sciences USA, 95: 9879-9884
[24] Wasmuth, J., Daub, J., Peregrın-Alvarez, J.M., Finney, C.A.M. and Parkinson, J. (2009). The origins of apicomplexan sequence innovation. Genome Research, 19:1202-1213
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