Author, Subjects, Keywords

Cited Author

 
 
   » By Author or Editor
 » Browse Author by Alphabet
 » By Journal
 » By Subjects
 » By Affiliations
 » By Type
 » By Year
 » By Latest Additions
 
 
   » By Author
 » Top 20 Authors
 » Top 20 Article
 » Top 20 Journal Cited
 » Top 20 Cited
 » Top 20 Author Cited
 » Usage Since Sept 2007


 
 
 

Login | Create Account

A Revisit into the DEN2 NS2B/NS3 Virus Protease Homology Model: Structural Verification and Comparison with Crystal Structure of HCV NS3/4A and DEN2 NS3

Lee, Yean Kee, and Rozana Othman, and Habibah A Wahab, and Rohana Yusof, and Noorsaadah Abd. Rahman, (2006) A Revisit into the DEN2 NS2B/NS3 Virus Protease Homology Model: Structural Verification and Comparison with Crystal Structure of HCV NS3/4A and DEN2 NS3. Malaysian Journal of Science, 25 (1). pp. 15-22. ISSN 13943065

Full text not available from this repository.

Official URL: http://ejum.fsktm.um.edu.my

Affiliations

University of Malaya. Faculty of Science. Dept. of Chemistry.
Universiti Sains Malaysia. School of Pharmaceutical Sciences.
University of Malaya. Faculty of Medicine. Dept. of Molecular Medicine.

Abstract

Although the crystal structure of DEN2 NS3 serine protease has been reported, the proteolytic mechanism of this enzyme in the presence of NS2B as co-factor which greatly enhances its activity is not well-understood. Using the homology model of DEN2 NS3 co-complexed with NS2B co-factor based on HCV NS3/4A as the proposed template, the model of the DEN2 NS2B/3 complex was reproduced and its structure evaluated through PROCHECK, VERIFY3D and ERRAT. Comparison of the homology model with the crystal structure of DEN2 NS3 revealed that this homology model served as a better choice for the NS2B/3 protein model in drug design.

Item Type:Journal
Keywords:Dengue, NS3, serine protease, structural verification, HCV
Subjects:Q Science, Computer Science
R Medicine, Dentistry, Pharmacy, Nursing
ID Code:2348

1. Bartenschlager, R., V. Lohman, T. Wilkinson, and J. O. Koch. (1995). Complex formation between the NS3 serine-type proteinase of the hepatitis C virus and NS4A and its importance for polyprotein maturation. J. Virol. 69: 7519-7528.

2. Bazan, J. F., and Fletterick, R. J. (1989). Detection of a trypsin-like serine protease domain in flaviviruses and pestiviruses. Virology 171: 637-639

3. Bowie, J. U., Luthy, R. and Eisenberg, D. (1991). A method to identify protein sequences that fold into a known three-dimensional structure. Science 253 (5016): 164-170

4. Brinkworth, R. I., D. P. Fairlie, D. Leung, and P. R. Young. (1999). Homology model of the dengue 2 virus NS3 protease: Putative interactions with both substrate and NS2B cofactor. J. Gen. Virol. 80: 1167-1177.

5. Chambers, T. J., Grakoui, A. and Rice, C. M. (1991). Processing of the yellow fever virus nonstructural polyprotein: A catalytically active NS3 proteinase domain and NS2B are required for cleavages at dibasic sites. J. Virol. 65 (11): 6042-6050.

6. Colovos, C. and Yeates, T. O. (1993). Verification of protein structures: patterns of nonbonded atomic interactions. Protein Sci. 2 (9): 1511-1519.

7. Falgout, B., Miller, R. H. and Lai, C.H. (1993). Deletion Analysis of Dengue Virus Type 4 Nonstructural Protein NS2B: Identification of a Domain Required for NS2B-NS3 Protease Activity. J. Virol. 67 (4): 2034-2042.

8. Gorbalenya, A. E., Donchenko, A. P., Koonin, E. V. and Blinov, V. M. (1989). N-terminal domains of putative helicases of flavi- and pestiviruses may be serine proteases. Nucleic Acids Res. 17 (10): 3889-3897.

9. Irie, K., Mohan, P. M., Sasaguri, Y., Putnak, R. and Padmanabhan, R. (1989). Sequence analysis of cloned dengue virus type 2 genome (New Guinea-C strain). Gene 75 (2): 197-211.

10. Kautner, I., Robinson, M. J. and Kuhnle, U. (1997). Dengue virus infection: Epidemiology, pathogenesis, clinical presentation, diagnosis, and prevention. J. Pediatr. 131 (4): 516-524.

11. Khumthong, R., Angsuthanasombat, C., Panyim S., and Katzenmeier, G. (2002). In vitro determination of dengue virus type 2 NS2B-NS3 protease activity with fluorescent peptide substrates. J. Biochem. Mol. Biol. 35 (2): 206-212.

12. Khumthong, R., P. Niyomrattanakit, S. Chanprapaph, C. Angsuthanasombat, S. Panyim and G. Katzenmeier. (2003). Steady-state cleavage kinetics for dengue virus type 2 NS2B-NS3(pro) serine protease with synthetic peptides. Protein Peptide Lett. 10 (1): 19-26.

13. Kim, J. L., K. A. Morgenstern, C. Lin, T. Fox, M. D. Dwyer, J. A. Landro, S. P. Chambers, Markland, W., Lepre, C. A., O'Malley, E. T., Harbeson, S. L., Rice, C. M., Murcko, M. A., Caron, P. R. and Thomson, J. A. (1996). Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell87 (2): 343-355.

14. Laskowski, R. A., MacArthur, M. W., Moss, D. S. & Thornton, J. M. (1993). PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Cryst. 26: 283-291.

15. Leung, D., Schroeder, K., White, H., Fang, N. X., Stoermer, M. J., Abbenante, G., Martin, J. L., Young, P. R. and Fairlie, D. P. (2001). Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates, and inhibitors. J. Biol. Chem. 276 (49): 45762-45771.

16. Li, H., Clum, S., You S., Ebner, K. E. and Padmanabhan, R. (1999). The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase functional domains of dengue virus type 2 NS3 converge within a region of 20 amino acids. J. Virol. 73 (4): 3108-3116.

17. Monath, T. P. (1994). Dengue: The risk to developed and developing countries. Proc. Natl. Acad. Sci. U. S. A. 91 (7): 2395-2400

18. Valle, R. P. C. and Falgout, B. (1998) Mutagenesis of the NS3 protease of dengue virus type 2. J. Viral. 72 (I): 624-632.

19. Yan, Y., Li, Y., Munshi, S., Sardana, V., Cole, J. L., Sardana, M., Steinkuehler, C., Tomei, L., De Francesco, R., Kuo, L. C. and Chen, Z. (1998). Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: A 2.2 Å resolution structure in a hexagonal crystal form. Protein Sci. 7 (4): 837-847.

20. Yusof, R., Clum, S., Wetzel, M., Murthy, H. M. and Padmanabhan, R. (2000) Purified NS2B/NS3 serine protease of dengue virus type 2 exhibits cofactor NS2B dependence for cleavage of substrates with dibasic amino acids in vitro. J. Biol. Chem. 275: 9963-9969.

Repository Staff Only: item control page
 
 
 
 
 
   
© Copyright 2007 MyAIS Faculty of Computer Science and Information Technology, University of Malaya – All Rights Reserved. Malaysian Abstracting and Indexing System is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.