Switching the Substrate Specificity of the Two-Component NS2B-NS3 Flavivirus Proteinase by Structure-Based Mutagenesis

  title={Switching the Substrate Specificity of the Two-Component NS2B-NS3 Flavivirus Proteinase by Structure-Based Mutagenesis},
  author={Sergey A. Shiryaev and Boris Ratnikov and Alexander E. Aleshin and Igor A. Kozlov and Nicholas A Nelson and Michal Lebl and Jeffrey W. Smith and Robert C. Liddington and Alex Y. Strongin},
  journal={Journal of Virology},
  pages={4501 - 4509}
ABSTRACT The flavivirus NS2B-NS3(pro)teinase is an essential element in the proteolytic processing of the viral precursor polyprotein and therefore a potential drug target. Recently, crystal structures and substrate preferences of NS2B-NS3pro from Dengue and West Nile viruses (DV and WNV) were determined. We established that the presence of Gly-Gly at the P1′-P2′ positions is optimal for cleavage by WNV NS3pro, whereas DV NS3pro tolerates well the presence of bulky residues at either P1′ or P2… 

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The authors' objectives were to define the substrate recognition pattern of the NS2B-NS3 protease of West Nile and Dengue virises and to represent a valuable biochemical resource and a solid foundation to support the design of selective substrates and synthetic inhibitors of flaviviral proteinases.

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