Structural features of NS3 of Dengue virus serotypes 2 and 4 in solution and insight into RNA binding and the inhibitory role of quercetin
| Autor: | Ardina Grüber, Shin Joon, Tsutomu Matsui, Malathy Sony Subramanian Manimekalai, Ankita Pan, Wuan Geok Saw, Thomas M. Weiss, Gerhard Grüber |
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| Přispěvatelé: | School of Biological Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation medicine.medical_treatment Hepatitis C virus viruses Dengue virus Viral Nonstructural Proteins 010402 general chemistry medicine.disease_cause 01 natural sciences Dengue 03 medical and health sciences Adenosine Triphosphate Allosteric Regulation X-Ray Diffraction Structural Biology Scattering Small Angle medicine Humans Amino Acid Sequence NS3 Protease biology Chemistry Flavivirus Helicase RNA virus diseases biochemical phenomena metabolism and nutrition Dengue Virus biology.organism_classification Virology RNA Helicase A Research Papers digestive system diseases 0104 chemical sciences Science::Biological sciences [DRNTU] 030104 developmental biology Biochemistry biology.protein Quercetin Sequence Alignment |
| Popis: | 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 forDengue virusserotypes 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 the174PPAVP179linker stretch of the relatedHepatitis 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. |
| Databáze: | OpenAIRE |
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