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Title: Structural features of NS3 of Dengue virus serotypes 2 and 4 in solution and insight into RNA binding and the inhibitory role of quercetin
Authors: Manimekalai, Malathy Sony Subramanian
Grüber, Ardina
Joon, Shin
Matsui, Tsutomu
Weiss, Thomas M.
Grüber, Gerhard
Pan, Ankita
Saw, Wuan Geok
Keywords: Dengue
DRNTU::Science::Biological sciences
Issue Date: 2017
Source: Pan, A., Saw, W. G., Manimekalai, M. S. S., Grüber, A., Joon, S., Matsui, T., . . . Grüber, G. (2017). Structural features of NS3 of Dengue virus serotypes 2 and 4 in solution and insight into RNA binding and the inhibitory role of quercetin. Acta Crystallographica Section D Structural Biology, 73(5), 402-419. doi:10.1107/S2059798317003849
Series/Report no.: Acta Crystallographica Section D Structural Biology
Abstract: Dengue virus (DENV), which has four serotypes (DENV‐1 to DENV‐4), is the causative agent of the viral infection dengue. DENV nonstructural protein 3 (NS3) comprises a serine protease domain and an RNA helicase domain which has nucleotide triphosphatase activities that are essential for RNA replication and viral assembly. Here, solution X‐ray scattering was used to provide insight into the overall structure and flexibility of the entire NS3 and its recombinant helicase and protease domains for Dengue virus serotypes 2 and 4 in solution. The DENV‐2 and DENV‐4 NS3 forms are elongated and flexible in solution. The importance of the linker residues in flexibility and domain–domain arrangement was shown by the compactness of the individual protease and helicase domains. Swapping of the 174PPAVP179 linker stretch of the related Hepatitis C virus (HCV) NS3 into DENV‐2 NS3 did not alter the elongated shape of the engineered mutant. Conformational alterations owing to RNA binding are described in the protease domain, which undergoes substantial conformational alterations that are required for the optimal catalysis of bound RNA. Finally, the effects of ATPase inhibitors on the enzymatically active DENV‐2 and DENV‐4 NS3 and the individual helicases are presented, and insight into the allosteric effect of the inhibitor quercetin is provided.
DOI: 10.1107/S2059798317003849
Schools: School of Biological Sciences 
Rights: © 2017 International Union of Crystallography. All rights reserved. This paper was published in Acta Crystallographica Section D Structural Biology and is made available with permission of International Union of Crystallography.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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