title: Structure-based mutational analysis of the NS3 helicase from dengue virus.
abstract: 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.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Aruna
authors.initials: A
authors.lastname: Sampath
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: Alex
authors.initials: A
authors.lastname: Chao
authors.forename: Dahai
authors.initials: D
authors.lastname: Luo
authors.forename: Julien
authors.initials: J
authors.lastname: Lescar
authors.forename: Subhash G
authors.initials: SG
authors.lastname: Vasudevan
mesh_terms: D000495:Allosteric Site / Q000235:genetics; D019943:Amino Acid Substitution; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry; D017354:Point Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D004791:Enzyme Inhibitors; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases