5yod | pdb_00005yod

Crystal structure of zika virus NS3 protease in complex with a small molecule inhibitor

spinqualitylabelsall models 5yod, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5yod is a 8 chain structure with sequence from Zikv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BEZ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Zika virus (ZIKV) infection has become a global public health concern. The viral NS2B-NS3 protease is an attractive antiviral target because of its role in maturation of viral non-structural proteins. Substrate-derived protease inhibitors have been investigated, but it remains challenging to develop them into drugs. Small-molecule inhibitors are of great interest in antiviral drug development. Here we report the structure and dynamics of ZIKV NS2B-NS3 protease covalently bound to a small-molecule inhibitor. Our crystallographic and NMR studies demonstrate that the inhibitor further stabilizes the closed conformation of ZIKV protease. Upon hydrolysis in situ into two fragments, the benzoyl group of the inhibitor forms a covalent bond with the side chain of catalytic residue S135, whereas the second fragment exhibits no obvious molecular interactions with the protease. This study provides a detailed mechanism of action for a covalent inhibitor, which will guide further development of ZIKV protease inhibitors. Structural Insights into the Inhibition of Zika Virus NS2B-NS3 Protease by a Small-Molecule Inhibitor.,Li Y, Zhang Z, Phoo WW, Loh YR, Li R, Yang HY, Jansson AE, Hill J, Keller TH, Nacro K, Luo D, Kang C Structure. 2018 Feb 21. pii: S0969-2126(18)30045-5. doi:, 10.1016/j.str.2018.02.005. PMID:29526431 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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