Open Access Open Access  Restricted Access Subscription or Fee Access

Computational Approach for Structure and Functionality Search for Hypothetical Proteins in Mycobacterium Leprae

Swapnil G. Sanmukh, Waman N. Paunikar, Tarun K. Ghosh

Abstract


Mycobacterium leprae Br4923 the causative agent of leprosy is one of the most puzzling and complex microorganism due to its gene decaying property and presence of large number of pseudogenes. The proper treatment of leprosy is not yet possible due to its drug resistance mechanism and uncultivable nature on culture media. The present work deals with the prediction of structure and function of hypothetical proteins in M. Leprae by the use of computational methods and bioinformatics. The prediction of orthologous sequence in biological sequence databases, assist in classification of 180 hypothetical protein sequences in their respective protein family by the use of web tools (CDD-BLAST, INTERPROSCAN, PFAM and COGs). The 3-D structures of the 160 functionally resolved hypothetical proteins were constructed using PS2 server (Protein structure prediction server). The generated data can prove useful in the prediction of evolutionary relationship of Mycobacterium leprae with those of other related Mycobacterium species. It may also assist in the designing of novel drug to treat leprosy.

Keywords


Gene Decay, Pseudogenes, Uncultivable, Web Tools, Evolutionary Relationship

Full Text:

PDF

References


Alex, B., Lachlan, C., Richard, D., Robert, D. F., Volker, H., Sam, G.J., Ajay, K., Mhairi, M., Simon, M., Erik, L. L. S., David, J. S., Corin Y., Sean, R. E., (2004). The Pfam families’ database. Nucleic Acids Research, Vol. 32, D138-D141.

Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., Zhang, Z., Miller, W., Lipman, D. J., (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25 (17), 3389-402.

Aron, M. Bauer., John, B. A., Myra, K. D., Carol, D. S., Noreen, R. G., Marc, G., Luning, H., Siqian, H., David, I. H., John, D. J., Zhaoxi, K., Dmitri, K., Christopher, J. L.,Cynthia A. L., Chunlei, L., Fu, L., Shennan, L., Gabriele, H. M., Mikhail, M., James, S. S., Narmada, T., Roxanne, A. Y., Jodie, J. Y., Dachuan, Z., Stephen, H. B., (2006). CDD: a conserved domain database for interactive domain family analysis. Nucleic Acids Research, Vol. 35, D237–D240.

Cédric, N., Desmond, G. H., Jaap, H., (2000). T-coffee: a novel method for fast and accurate multiple sequence alignment. J. Mol. Biol. 302, 205-217.

Chih-Chieh, C., Jenn-Kang, H., Jinn-Moon, Y., (2006). PS2: protein structure prediction server Nucl. Acids Res. 34, W152-W157.

Cole ST, Brosch R, Parkhill J, et al. (1998). "Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence". Nature 393 (6685): 537–44. doi:10.1038/31159.

Cole ST, Eiglmeier K, Parkhill J, et al. (2001). "Massive gene decay in the leprosy bacillus". Nature 409 (6823): 1007–11. doi:10.1038/35059006.

Dilip, G., Alankar, R., (2009). Computational Function and Structural Annotations for Hypothetical Proteins Bacillus anthracis. Biofrontiers, 1, 27-36.

Edward, E., Gary, L. G., Osnat, H., John, M., John, O., Roberto, J. P., Linda, B., Delwood, R., Andrew, J. H., (2000). Biological function made crystal clear- annotation of hypothetical proteins via structural genomics. Current Opinion in Biotechnology 11, 25-30.

Hansen GHA (1874). "Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy)" (in Norwegian). Norsk Mag. Laegervidenskaben 4: 1–88.

Irgens L (2002). "The discovery of the leprosy bacillus". Tidsskr nor Laegeforen 122 (7): 708–9.

Marc Monot, Nadine Honoré, Thierry Garnier, Nora Zidane, Diana Sherafi, Alberto Paniz-Mondolfi, Masanori Matsuoka, G Michael Taylor, Helen D Donoghue, Abi Bouwman, Simon Mays, Claire Watson, Diana Lockwood, Ali Khamesipour, Yahya Dowlati, Shen Jianping, Thomas H Rea, Lucio Vera-Cabrera, Mariane M Stefani, Sayera Banu, Murdo Macdonald, Bishwa Raj Sapkota, John S Spencer, Jérôme Thomas, Keith Harshman, Pushpendra Singh, Philippe Busso, Alexandre Gattiker, Jacques Rougemont, Patrick J Brennan & Stewart T Cole (2009). Comparative genomic and phylogeographic analysis of Mycobacterium leprae, 41 (12), 1282-1291.Nature Genetics

McMurray DN (1996). Mycobacteria and Nocardia. In: Baron's Medical Microbiology (Baron S et al., Ed.) (http:/ / www. ncbi. nlm. nih. gov/ books/ bv. fcgi?rid=mmed. section. 1833) (4th ed.). Univ of Texas Medical Branch.

Roman, L. T., Michael, Y., Galperin, Darren A. Natale, Eugene V. Koonin (2000). The COG database: a tool for genome –scale analysis of protein functions and evolution. Nucleic Acid Research. 28, 33-36.

Ryan, K, J., Ray, CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 451–3.

Schaffer, A. A., Aravind, L., Madden, T. L., Shavirin, S., Spouge, J.L., Wolf, Y. I., Koonin, E. V., Altschul., S. F., (2001). Improving the accuracy of PSI-BLAST protein database searches with Composition-based statistics and other refinements. Nucleic Acids Res. 29(14), 2994-3005.

Truman RW, Krahenbuhl JL (2001). "Viable M. leprae as a research reagent". Int. J. Lepr. Other Mycobact. Dis. 69 (1): 1–12.

Wendy, B., Alexander, V.D.B., Evelyn, C., Pascal, H., Peter, S., Guenter, S., Mary, A. T., (2000). The EMBL Nucleotide Sequence Database. Nucleic Acid Research. 28, 19-23

Williams, D. L., Oby-Robinson, S., Pittman, T. L., Scollard, D. M. 2003. Purification of Mycobacterium leprae RNA for gene expression analysis from leprosy biopsy specimens. BioTechniques 35:534–536.

Zafer, A., Yucel, A., Mark, B., (2006). Protein secondary structure prediction for a single-sequence using hidden semi-Markov models, BMC Bioinformatics, 7, 178.

Zdobnov, E. M., Rolf, A., (2001). Interproscan- an integration platform for the signatures recognition methods in InterPro. Bioinformatics 17, 847-848


Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.