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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, Ting Xu,^2, Alex Chao,¹ Dahai Luo,² Julien Lescar,^2* and Subhash G. Vasudevan^1*

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.

These two authors contributed equally to this work.

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