4rna

Crystal structure of PLpro from Middle East Respiratory Syndrome (MERS) coronavirus

spinqualitylabelsall models 4rna, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rna 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 1.794Å Ligands: CSS, OCS, PO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function K4LC41_MERS Publication Abstract from PubMed The Middle East Respiratory Syndrome coronavirus (MERS-CoV) papain-like protease (PLpro) blocking loop 2 (BL2) structure differs significantly from that of SARS-CoV PLpro, where it has been proven to play a crucial role in SARS-CoV PLpro inhibitor binding. Four SARS-CoV PLpro lead inhibitors were tested against MERS-CoV PLpro, none of which were effective against MERS-CoV PLpro. Structure and sequence alignments revealed that two residues, Y269 and Q270, responsible for inhibitor binding to SARS-CoV PLpro, were replaced by T274 and A275 in MERS-CoV PLpro, making critical binding interactions difficult to form for similar types of inhibitors. High-throughput screening (HTS) of 25000 compounds against both PLpro enzymes identified a small fragment-like noncovalent dual inhibitor. Mode of inhibition studies by enzyme kinetics and competition surface plasmon resonance (SPR) analyses suggested that this compound acts as a competitive inhibitor with an IC50 of 6 muM against MERS-CoV PLpro, indicating that it binds to the active site, whereas it acts as an allosteric inhibitor against SARS-CoV PLpro with an IC50 of 11 muM. These results raised the possibility that inhibitor recognition specificity of MERS-CoV PLpro may differ from that of SARS-CoV PLpro. In addition, inhibitory activity of this compound was selective for SARS-CoV and MERS-CoV PLpro enzymes over two human homologues, the ubiquitin C-terminal hydrolases 1 and 3 (hUCH-L1 and hUCH-L3). Inhibitor Recognition Specificity of MERS-CoV Papain-like Protease May Differ from That of SARS-CoV.,Lee H, Lei H, Santarsiero BD, Gatuz JL, Cao S, Rice AJ, Patel K, Szypulinski MZ, Ojeda I, Ghosh AK, Johnson ME ACS Chem Biol. 2015 Mar 16. PMID:25746232 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus protease 3D structures

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