About: Inhibitor Recognition Specificity of MERS-CoV Papain-like Protease May Differ from That of SARS-CoV

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Inhibitor Recognition Specificity of MERS-CoV Papain-like Protease May Differ from That of SARS-CoV
Creator	Lee, Hyun Ojeda, Isabel Patel, Kavankumar Johnson, Michael Cao, Shuyi Lei, Hao Gatuz, Joseph Ghosh, Arun Rice, Amy Santarsiero, Bernard Szypulinski, Michael
source	Medline; PMC
abstract	[Image: see text] 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 25 000 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 IC(50) of 6 μM 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 IC(50) of 11 μM. 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).
has issue date	2015-03-06(xsd:dateTime)
bibo:doi	10.1021/cb500917m
bibo:pmid	25746232
has license	bronze-oa
sha1sum (hex)	1f245f2e3e8fa0a1b48bee7114b782405ed2381e
schema:url	https://doi.org/10.1021/cb500917m
resource representing a document's title	Inhibitor Recognition Specificity of MERS-CoV Papain-like Protease May Differ from That of SARS-CoV
has PubMed Central identifier	PMC4845099
has PubMed identifier	25746232
schema:publication	ACS Chemical Biology
resource representing a document's body	covid:1f245f2e3e8fa0a1b48bee7114b782405ed2381e#body_text
is schema:about of	named entity 'PROTEASE' named entity 'SPECIFICITY' named entity 'INHIBITOR' named entity 'PAPAIN' named entity 'LIKE' named entity 'MERS-COV' named entity 'RECOGNITION' named entity 'SUPPORTING INFORMATION' named entity 'SARS-COV' named entity 'MERS-CoV' named entity 'TCEP' named entity 'enzyme activity' named entity 'mutagenesis' named entity 'Site-Directed Mutagenesis' named entity 'pH 8' named entity 'NaCl' named entity 'SARS' named entity 'enzyme reaction' named entity 'Imidazole' named entity 'protease' named entity 'pH 8' named entity 'β-mercaptoethanol' named entity 'enzyme' named entity 'cleavage site' named entity 'GE Healthcare' named entity 'His-tagged' named entity 'NaCl' named entity 'wild-type' named entity 'positive control' named entity 'Novagen' named entity 'enzyme' named entity 'inhibitory activity' named entity 'PLpro' named entity 'AMC' named entity '7.5' named entity 'PLpro' named entity 'K i' named entity 'over-expressed' named entity 'pH 8' named entity 'lysed' named entity 'protease inhibitor' named entity 'serial dilution' named entity 'Imidazole' named entity 'LC/MS' named entity 'gradient' named entity 'BSA' named entity 'NMR' named entity 'NaCl' named entity 'Sigmaplot' named entity 'His-tag' named entity 'over-expressed' named entity 'Tris-HCl' named entity 'protein' named entity 'NMR' named entity 'NMR' named entity 'concentration-response curve' named entity 'enzyme' named entity 'protease' named entity 'substrate' named entity 'Protein' named entity 'DMSO' named entity 'IPTG' named entity 'Triton X-100' named entity 'chemical library' named entity 'crystallization' named entity 'gene synthesis' named entity 'DMSO' named entity 'HPLC' named entity 'sonication' named entity 'lysis buffer' named entity 'substrate'

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