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: 2317 Downloads: 907
[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
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