2vbc
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CRYSTAL STRUCTURE OF THE NS3 PROTEASE-HELICASE FROM DENGUE VIRUS
OverviewOverview
Several flaviviruses are important human pathogens including dengue virus, a disease against which neither a vaccine nor specific antiviral therapies, currently exist. During infection, the flavivirus RNA genome is translated, into a polyprotein, which is cleaved into several components. The, non-structural protein 3 (NS3) carries out enzymatic reactions essential, for viral replication, including proteolysis of the polyprotein through, its serine-protease N-terminal domain, with a segment of 40 residues from, the NS2B protein acting as a cofactor. The ATPase/helicase domain is, located at the C-terminus of NS3. Atomic structures are available for, these domains separately but a molecular view of the full length, flavivirus NS3 polypeptide is still lacking. We report a crystallographic, structure at 3.15 A resolution of a complete NS3 molecule fused to 18, residues of the NS2B cofactor. The relative orientation between the, protease and helicase domains is drastically different compared to the, scNS3-NS4A molecule from hepatitis C virus (HCV), which was caught in the, act of cis cleavage at the NS3-NS4A junction. Here, the protease domain, sits beneath the ATP binding site, giving the molecule an elongated shape., The domain arrangement found in the crystal structure fits nicely into an, envelope determined ab-initio using small angle X-ray scattering, experiments in solution, suggesting a stable molecular conformation. We, propose that a basic patch located at the surface of the protease domain, increases the affinity for nucleotides and could also participate in RNA, binding, explaining the higher unwinding activity of the full-length, enzyme compared to the isolated helicase domain.
About this StructureAbout this Structure
2VBC is a Protein complex structure of sequences from Dengue virus 4. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the NS3 protease-helicase from Dengue virus., Luo D, Xu T, Hunke C, Gruber G, Vasudevan SG, Lescar J, J Virol. 2007 Oct 17;. PMID:17942558
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