2ijo | pdb_00002ijo

Crystal Structure of the West Nile virus NS2B-NS3 protease complexed with bovine pancreatic trypsin inhibitor

spinqualitylabelsall models 2ijo, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ijo is a 3 chain structure with sequence from Bos taurus and Wnv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 2fom, 2fp7, 2ggv Activity: Flavivirin, with EC number 3.4.21.91 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [BPT1_BOVIN] Inhibits trypsin, kallikrein, chymotrypsin, and plasmin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Pathogenic members of the flavivirus family, including West Nile Virus (WNV) and Dengue Virus (DV), are growing global threats for which there are no specific treatments. The two-component flaviviral enzyme NS2B-NS3 cleaves the viral polyprotein precursor within the host cell, a process that is required for viral replication. Here, we report the crystal structure of WNV NS2B-NS3pro both in a substrate-free form and in complex with the trypsin inhibitor aprotinin/BPTI. We show that aprotinin binds in a substrate-mimetic fashion in which the productive conformation of the protease is fully formed, providing evidence for an "induced fit" mechanism of catalysis and allowing us to rationalize the distinct substrate specificities of WNV and DV proteases. We also show that the NS2B cofactor of WNV can adopt two very distinct conformations and that this is likely to be a general feature of flaviviral proteases, providing further opportunities for regulation. Finally, by comparing the flaviviral proteases with the more distantly related Hepatitis C virus, we provide insights into the evolution of the Flaviviridae fold. Our work should expedite the design of protease inhibitors to treat a range of flaviviral infections. Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold.,Aleshin AE, Shiryaev SA, Strongin AY, Liddington RC Protein Sci. 2007 May;16(5):795-806. Epub 2007 Mar 30. PMID:17400917 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Basic Pancreatic Trypsin Inhibitor

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