4p16

Crystal structure of the papain-like protease of Middle-East Respiratory Syndrome coronavirus

spinqualitylabelsall models 4p16, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p16 is a 1 chain structure with sequence from Human betacoronavirus 2c EMC/2012. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: CME, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function K0BWD0_MERS Publication Abstract from PubMed The Middle-East Respiratory Syndrome coronavirus (MERS-CoV) causes severe acute pneumonia and renal failure. The MERS-CoV papain-like protease (PLpro) is a potential target for the development of antiviral drugs. To facilitate these efforts, we determined the three-dimensional structure of the enzyme by X-ray crystallography. The molecule consists of a ubiquitin-like domain and a catalytic core domain. The catalytic domain displays an extended right-hand fold with a zinc ribbon and embraces a solvent-exposed substrate-binding region. The overall structure of the MERS-CoV PLpro is similar to that of the corresponding SARS-CoV enzyme, but the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites differ from the latter. These differences are the likely reason for reduced in vitro peptide hydrolysis and deubiquitinating activities of the MERS-CoV PLpro, compared to the homologous enzyme from the SARS coronavirus. Introduction of a side-chain capable of oxyanion stabilization through the Leu106Trp mutation greatly enhances the in vitro catalytic activity of the MERS-CoV PLpro. The unique features observed in the crystal structure of the MERS-CoV PLpro should allow the design of antivirals that would not interfere with host ubiquitin-specific proteases. Crystal structure of the papain-like protease of MERS coronavirus reveals unusual, potentially druggable active-site features.,Lei J, Mesters JR, Drosten C, Anemuller S, Ma Q, Hilgenfeld R Antiviral Res. 2014 Jun 30;109C:72-82. doi: 10.1016/j.antiviral.2014.06.011. PMID:24992731 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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