This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sampath, A.
Right arrow Articles by Vasudevan, S. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sampath, A.
Right arrow Articles by Vasudevan, S. G.

 Previous Article  |  Next Article 

Journal of Virology, July 2006, p. 6686-6690, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.02215-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Structure-Based Mutational Analysis of the NS3 Helicase from Dengue Virus

Aruna Sampath,1,{dagger} Ting Xu,2,{dagger} Alex Chao,1 Dahai Luo,2 Julien Lescar,2* and Subhash G. Vasudevan1*

Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos Building, Singapore 138670, Singapore,1 School of Biological Sciences, Nanyang Technological University, 60, Nanyang Drive, Singapore 637551, Singapore2

Received 20 October 2005/ Accepted 10 April 2006

We performed a mutational analysis of the NS3 helicase of dengue virus to test insights gleaned from its crystal structure and identified four residues in the full-length protein that severely impaired either its RTPase and ATPase (Arg-457-458, Arg-460, Arg-463) or helicase (Ile-365, Arg-376) activity. Alanine substitution of Lys-396, which is located at the surface of domain II, drastically reduced all three enzymatic activities. Our study points to a pocket at the surface of domain II that may be suitable for the design of allosteric inhibitors.

* Corresponding author. Mailing address for Julien Lescar: School of Biological Sciences, Nanyang Technological University, 60, Nanyang Drive, Singapore 637551, Singapore. E-mail: julien{at}ntu.edu.sg. Mailing address for Subhash Vasudevan: Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos Building, Singapore 138670, Singapore. Phone: 65 67222909. Fax: 011-65-67222916. E-mail: subhash.vasudevan{at}novartis.com.

{dagger} These two authors contributed equally to this work.

Journal of Virology, July 2006, p. 6686-6690, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.02215-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chernov, A. V., Shiryaev, S. A., Aleshin, A. E., Ratnikov, B. I., Smith, J. W., Liddington, R. C., Strongin, A. Y. (2008). The Two-component NS2B-NS3 Proteinase Represses DNA Unwinding Activity of the West Nile Virus NS3 Helicase. J. Biol. Chem. 283: 17270-17278 [Abstract] [Full Text]  
  • Luo, D., Xu, T., Hunke, C., Gruber, G., Vasudevan, S. G., Lescar, J. (2008). Crystal Structure of the NS3 Protease-Helicase from Dengue Virus. J. Virol. 82: 173-183 [Abstract] [Full Text]  
  • Yap, T. L., Xu, T., Chen, Y.-L., Malet, H., Egloff, M.-P., Canard, B., Vasudevan, S. G., Lescar, J. (2007). Crystal Structure of the Dengue Virus RNA-Dependent RNA Polymerase Catalytic Domain at 1.85-Angstrom Resolution. J. Virol. 81: 4753-4765 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»