COMPUTATIONAL 3D STRUCTURE PREDICTION, EVALUATION AND ANALYSIS OF PYRUVATE DEHYDROGENASE AN EFFECTIVE TARGET FOR FILARIAL INFECTION BY BRUGIA PAHANGI USING HOMOLOGY MODELING APPROACH

  • Shailesh Kumar Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan India
  • Onkar Nath Jaipur National University, Jaipur, Rajasthan, India
  • Sumit Govil Jaipur National University, Jaipur, Rajasthan, India
  • A. N. Pathak Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan India

Abstract

Pyruvate dehydrogenase protein is a part of cellular respiration which helps in maintaining glucose and energy level (ATP) in the cells for their normal functioning. Initially it was reported that Brugia pahangi is a nematode causing filarial infections in animals like dogs and cats. But, in the recent studies, Brugia pahangiis also found to cause filarial infections in Humans, in Kuala Lumpur, Malaysia. By targeting the cellular respiration of this worm this filarial infections can be treated. The three dimensional structure of pyruvate dehydrogenase in B.pahangi will help to target cellular respiration more efficiently. The comparative modeling approach based software Modeller9.13 is used to model three dimensional structure of pyruvate dehydrogenase. The modeled structure was evaluated by Procheck, VADAR, Process, ProSA tools. The Physiochemical properties of this protein are analyzed by APD2 and Protparam software. Enzymatic Cleavage site of this protein is identified by Peptide cutter tool. Active sites in modeled structure are identified by Pocket finder tool fordrug targets.The modeled structure, properties and active sites of this protein will help to design lead molecules which can treat the filarial infections in humans. The structure will also help to understand the working of pyruvate dehydrogenase in betterand efficient manner by identifying the protein interaction networks in Brugia pahangi.

Keywords: Filarial, Comparative modelling, Active site, Procheck, Cleavage Site, interaction networks

Downloads

Download data is not yet available.

References

1. Jeong JY, Jeoung NH, Park KG, Lee IK. Transcriptional regulation of pyruvate dehydrogenase kinase. Diabetes & Metabolism Journal 2012; 36(5):328-335.
2. Li BW, Rush AC, Mitreva M, Yin Y, Spiro D, Ghedin E, Weil GJ. Transcriptomes and pathways associated with infectivity, survival and immunogenicity in Brugia malayi L3. BMC Genomics 2009; 10(1):267.
3. Muslim A, Fong MY, Mahmud R, Lau YL, Sivanandam S. Armigeres subalbatus incriminated as a vector of zoonotic Brugia pahangi filariasis in suburban Kuala Lumpur, Peninsular Malaysia. Parasites & Vectors 2013; 6(1): 219.
4. Middleton KR, Saz HJ. Comparative utilization of pyruvate by Brugia pahangi, Dipetalonema viteae, and Litomosoides carinii. The Journal of Parasitology 1979; 1-7.
5. Eswar N, Eramian D, Webb B, Shen MY, Sali A. Protein structure modeling with MODELLER. Structural Proteomics. Humana Press. 2008:145-159.
6. Laskowski RA, MacArthur MW, Moss DS & Thornton, J. M. PROCHECK: a program to check the stereochemical quality of protein structures. Journal of applied Crystallography 1993; 26(2):283-291.
7. Wiederstein M, Manfred JS. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Research 2007; 35 suppl 2: W407-W410.
8. Willard L, Ranjan A, Zhang H, Monzavi H, Boyko RF, Sykes BD, Wishart DS. VADAR: a web server for quantitative evaluation of protein structure quality. Nucleic acids research 2003; 31(13); 3316-3319.
9. Wang Z, Guangshun W. APD: the antimicrobial peptide database."Nucleic Acids Research. 2004; 32(1):D590-D592.
10. Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Bairoch A. Protein Identification and Analysis Tools on the ExPASy Server; (In) John M. Walker (ed): The Proteomics Protocols Handbook, Humana Press. 2005, pp. 571-607.
11. Laurie, Alasdair TR, and Richard MJ. Q-SiteFinder: an energy-based method for the prediction of protein–ligand binding sites. Bioinformatics 2005; 21(9):1908-1916.
12. Burgoyne NJ, Jackson RM. Predicting protein interaction sites: binding hot-spots in protein-protein and protein-ligand interfaces. Bioinformatics 2006; 22:1335-1342.
13. Willard L, Ranjan A, Zhang H, Monzavi H, Boyko RF, Sykes BD, Wishart DS. VADAR: a web server for quantitative evaluation of protein structure quality. Nucleic Acids Res. 2003; 31 (13):3316-3319.
14. Negi SS, Schein CH, Oezguen N, Power TD, Braun W. InterProSurf: a web server for predicting interacting sites on protein surfaces. Bioinformatics 2007; 23(24):3397-3399.
Statistics
189 Views | 255 Downloads
How to Cite
Kumar, S., O. Nath, S. Govil, and A. N. Pathak. “COMPUTATIONAL 3D STRUCTURE PREDICTION, EVALUATION AND ANALYSIS OF PYRUVATE DEHYDROGENASE AN EFFECTIVE TARGET FOR FILARIAL INFECTION BY BRUGIA PAHANGI USING HOMOLOGY MODELING APPROACH”. International Journal of Pharmaceutical Sciences and Drug Research, Vol. 6, no. 2, Apr. 2014, pp. 120-3, http://www.ijpsdr.com/index.php/ijpsdr/article/view/316.
Section
Research Article