Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses
Identifieur interne : 001373 ( Pmc/Curation ); précédent : 001372; suivant : 001374Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses
Auteurs : Chi-Pang Chuck [République populaire de Chine] ; Hak-Fun Chow [République populaire de Chine] ; David Chi-Cheong Wan [République populaire de Chine] ; Kam-Bo Wong [République populaire de Chine]Source :
- PLoS ONE [ 1932-6203 ] ; 2011.
Abstract
Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CLpro), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection.
Here, we profiled the substrate specificities of 3CLpro from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS-CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 19×8 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CLpro prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CLpro from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CLpro prefers P4-Pro and SARS-CoV 3CLpro prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences ‘VARLQ↓SGF’ that can be cleaved efficiently by all 3CLpro with relative activity of 1.7 to 3.2, and ‘VPRLQ↓SGF’ that can be cleaved specifically by IBV 3CLpro with relative activity of 4.3.
The comprehensive substrate specificities of 3CLpro from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases.
Url:
DOI: 10.1371/journal.pone.0027228
PubMed: 22073294
PubMed Central: 3206940
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001373
Links to Exploration step
PMC:3206940Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses</title><author><name sortKey="Chuck, Chi Pang" sort="Chuck, Chi Pang" uniqKey="Chuck C" first="Chi-Pang" last="Chuck">Chi-Pang Chuck</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Life Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea></affiliation></author><author><name sortKey="Chow, Hak Fun" sort="Chow, Hak Fun" uniqKey="Chow H" first="Hak-Fun" last="Chow">Hak-Fun Chow</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Chemistry, The Chinese University of Hong Kong, Hong Kong, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Chemistry, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea></affiliation></author><author><name sortKey="Wan, David Chi Cheong" sort="Wan, David Chi Cheong" uniqKey="Wan D" first="David Chi-Cheong" last="Wan">David Chi-Cheong Wan</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea></affiliation></author><author><name sortKey="Wong, Kam Bo" sort="Wong, Kam Bo" uniqKey="Wong K" first="Kam-Bo" last="Wong">Kam-Bo Wong</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Life Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22073294</idno><idno type="pmc">3206940</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206940</idno><idno type="RBID">PMC:3206940</idno><idno type="doi">10.1371/journal.pone.0027228</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">001373</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001373</idno><idno type="wicri:Area/Pmc/Curation">001373</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001373</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses</title><author><name sortKey="Chuck, Chi Pang" sort="Chuck, Chi Pang" uniqKey="Chuck C" first="Chi-Pang" last="Chuck">Chi-Pang Chuck</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Life Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea></affiliation></author><author><name sortKey="Chow, Hak Fun" sort="Chow, Hak Fun" uniqKey="Chow H" first="Hak-Fun" last="Chow">Hak-Fun Chow</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Chemistry, The Chinese University of Hong Kong, Hong Kong, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Chemistry, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea></affiliation></author><author><name sortKey="Wan, David Chi Cheong" sort="Wan, David Chi Cheong" uniqKey="Wan D" first="David Chi-Cheong" last="Wan">David Chi-Cheong Wan</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea></affiliation></author><author><name sortKey="Wong, Kam Bo" sort="Wong, Kam Bo" uniqKey="Wong K" first="Kam-Bo" last="Wong">Kam-Bo Wong</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Life Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CL<sup>pro</sup>), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection.</p></sec><sec><title>Methodology/Principal Findings</title><p>Here, we profiled the substrate specificities of 3CL<sup>pro</sup> from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS-CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 19×8 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CL<sup>pro</sup> prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CL<sup>pro</sup> from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CL<sup>pro</sup> prefers P4-Pro and SARS-CoV 3CL<sup>pro</sup> prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences ‘VARLQ↓SGF’ that can be cleaved efficiently by all 3CL<sup>pro</sup> with relative activity of 1.7 to 3.2, and ‘VPRLQ↓SGF’ that can be cleaved specifically by IBV 3CL<sup>pro</sup> with relative activity of 4.3.</p></sec><sec><title>Conclusions/Significance</title><p>The comprehensive substrate specificities of 3CL<sup>pro</sup> from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L van der Hoek</name></author><author><name sortKey="Pyrc, K" uniqKey="Pyrc K">K Pyrc</name></author><author><name sortKey="Jebbink, Mf" uniqKey="Jebbink M">MF Jebbink</name></author><author><name sortKey="Vermeulen Oost, W" uniqKey="Vermeulen Oost W">W Vermeulen-Oost</name></author><author><name sortKey="Berkhout, Rj" uniqKey="Berkhout R">RJ Berkhout</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hamre, D" uniqKey="Hamre D">D Hamre</name></author><author><name sortKey="Procknow, Jj" uniqKey="Procknow J">JJ Procknow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Chu, Cm" uniqKey="Chu C">CM Chu</name></author><author><name sortKey="Chan, Kh" uniqKey="Chan K">KH Chan</name></author><author><name sortKey="Tsoi, Hw" uniqKey="Tsoi H">HW Tsoi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuiken, T" uniqKey="Kuiken T">T Kuiken</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author><author><name sortKey="Schutten, M" uniqKey="Schutten M">M Schutten</name></author><author><name sortKey="Rimmelzwaan, Gf" uniqKey="Rimmelzwaan G">GF Rimmelzwaan</name></author><author><name sortKey="Van Amerongen, G" uniqKey="Van Amerongen G">G van Amerongen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Lai, St" uniqKey="Lai S">ST Lai</name></author><author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Yam, Ly" uniqKey="Yam L">LY Yam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheever, Fs" uniqKey="Cheever F">FS Cheever</name></author><author><name sortKey="Daniels, Jb" uniqKey="Daniels J">JB Daniels</name></author><author><name sortKey="Pappenheimer, Am" uniqKey="Pappenheimer A">AM Pappenheimer</name></author><author><name sortKey="Bailey, Ot" uniqKey="Bailey O">OT Bailey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Binn, Ln" uniqKey="Binn L">LN Binn</name></author><author><name sortKey="Lazar, Ec" uniqKey="Lazar E">EC Lazar</name></author><author><name sortKey="Keenan, Kp" uniqKey="Keenan K">KP Keenan</name></author><author><name sortKey="Huxsoll, Dl" uniqKey="Huxsoll D">DL Huxsoll</name></author><author><name sortKey="Marchwicki, Rh" uniqKey="Marchwicki R">RH Marchwicki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name></author><author><name sortKey="Chu, Dk" uniqKey="Chu D">DK Chu</name></author><author><name sortKey="Chan, Kh" uniqKey="Chan K">KH Chan</name></author><author><name sortKey="Wong, Ok" uniqKey="Wong O">OK Wong</name></author><author><name sortKey="Ellis, Tm" uniqKey="Ellis T">TM Ellis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beaudette, Fr" uniqKey="Beaudette F">FR Beaudette</name></author><author><name sortKey="Hudson, Cb" uniqKey="Hudson C">CB Hudson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Doyle, Lp" uniqKey="Doyle L">LP Doyle</name></author><author><name sortKey="Hutchings, Lm" uniqKey="Hutchings L">LM Hutchings</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tyrrell, Da" uniqKey="Tyrrell D">DA Tyrrell</name></author><author><name sortKey="Bynoe, Ml" uniqKey="Bynoe M">ML Bynoe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snijder, Ej" uniqKey="Snijder E">EJ Snijder</name></author><author><name sortKey="Bredenbeek, Pj" uniqKey="Bredenbeek P">PJ Bredenbeek</name></author><author><name sortKey="Dobbe, Jc" uniqKey="Dobbe J">JC Dobbe</name></author><author><name sortKey="Thiel, V" uniqKey="Thiel V">V Thiel</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J Ziebuhr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gorbalenya, Ae" uniqKey="Gorbalenya A">AE Gorbalenya</name></author><author><name sortKey="Snijder, Ej" uniqKey="Snijder E">EJ Snijder</name></author><author><name sortKey="Spaan, Wj" uniqKey="Spaan W">WJ Spaan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gaunt, Er" uniqKey="Gaunt E">ER Gaunt</name></author><author><name sortKey="Hardie, A" uniqKey="Hardie A">A Hardie</name></author><author><name sortKey="Claas, Ec" uniqKey="Claas E">EC Claas</name></author><author><name sortKey="Simmonds, P" uniqKey="Simmonds P">P Simmonds</name></author><author><name sortKey="Templeton, Ke" uniqKey="Templeton K">KE Templeton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dominguez, Sr" uniqKey="Dominguez S">SR Dominguez</name></author><author><name sortKey="Robinson, Cc" uniqKey="Robinson C">CC Robinson</name></author><author><name sortKey="Holmes, Kv" uniqKey="Holmes K">KV Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cavanagh, D" uniqKey="Cavanagh D">D Cavanagh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ignjatovic, J" uniqKey="Ignjatovic J">J Ignjatovic</name></author><author><name sortKey="Sapats, S" uniqKey="Sapats S">S Sapats</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Cw" uniqKey="Lin C">CW Lin</name></author><author><name sortKey="Tsai, Ch" uniqKey="Tsai C">CH Tsai</name></author><author><name sortKey="Tsai, Fj" uniqKey="Tsai F">FJ Tsai</name></author><author><name sortKey="Chen, Pj" uniqKey="Chen P">PJ Chen</name></author><author><name sortKey="Lai, Cc" uniqKey="Lai C">CC Lai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, H" uniqKey="Yang H">H Yang</name></author><author><name sortKey="Xie, W" uniqKey="Xie W">W Xie</name></author><author><name sortKey="Xue, X" uniqKey="Xue X">X Xue</name></author><author><name sortKey="Yang, K" uniqKey="Yang K">K Yang</name></author><author><name sortKey="Ma, J" uniqKey="Ma J">J Ma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Sy" uniqKey="Li S">SY Li</name></author><author><name sortKey="Chen, C" uniqKey="Chen C">C Chen</name></author><author><name sortKey="Zhang, Hq" uniqKey="Zhang H">HQ Zhang</name></author><author><name sortKey="Guo, Hy" uniqKey="Guo H">HY Guo</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, Cy" uniqKey="Wu C">CY Wu</name></author><author><name sortKey="Jan, Jt" uniqKey="Jan J">JT Jan</name></author><author><name sortKey="Ma, Sh" uniqKey="Ma S">SH Ma</name></author><author><name sortKey="Kuo, Cj" uniqKey="Kuo C">CJ Kuo</name></author><author><name sortKey="Juan, Hf" uniqKey="Juan H">HF Juan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name></author><author><name sortKey="Gui, C" uniqKey="Gui C">C Gui</name></author><author><name sortKey="Luo, X" uniqKey="Luo X">X Luo</name></author><author><name sortKey="Yang, Q" uniqKey="Yang Q">Q Yang</name></author><author><name sortKey="Gunther, S" uniqKey="Gunther S">S Gunther</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fan, K" uniqKey="Fan K">K Fan</name></author><author><name sortKey="Ma, L" uniqKey="Ma L">L Ma</name></author><author><name sortKey="Han, X" uniqKey="Han X">X Han</name></author><author><name sortKey="Liang, H" uniqKey="Liang H">H Liang</name></author><author><name sortKey="Wei, P" uniqKey="Wei P">P Wei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goetz, Dh" uniqKey="Goetz D">DH Goetz</name></author><author><name sortKey="Choe, Y" uniqKey="Choe Y">Y Choe</name></author><author><name sortKey="Hansell, E" uniqKey="Hansell E">E Hansell</name></author><author><name sortKey="Chen, Yt" uniqKey="Chen Y">YT Chen</name></author><author><name sortKey="Mcdowell, M" uniqKey="Mcdowell M">M McDowell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chuck, Cp" uniqKey="Chuck C">CP Chuck</name></author><author><name sortKey="Chong, Lt" uniqKey="Chong L">LT Chong</name></author><author><name sortKey="Chen, C" uniqKey="Chen C">C Chen</name></author><author><name sortKey="Chow, Hf" uniqKey="Chow H">HF Chow</name></author><author><name sortKey="Wan, Dc" uniqKey="Wan D">DC Wan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hegyi, A" uniqKey="Hegyi A">A Hegyi</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J Ziebuhr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, S" uniqKey="Lee S">S Lee</name></author><author><name sortKey="Tikhomirova, A" uniqKey="Tikhomirova A">A Tikhomirova</name></author><author><name sortKey="Shalvardjian, N" uniqKey="Shalvardjian N">N Shalvardjian</name></author><author><name sortKey="Chalikian, Tv" uniqKey="Chalikian T">TV Chalikian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kyte, J" uniqKey="Kyte J">J Kyte</name></author><author><name sortKey="Doolittle, Rf" uniqKey="Doolittle R">RF Doolittle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chou, Py" uniqKey="Chou P">PY Chou</name></author><author><name sortKey="Fasman, Gd" uniqKey="Fasman G">GD Fasman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xue, X" uniqKey="Xue X">X Xue</name></author><author><name sortKey="Yu, H" uniqKey="Yu H">H Yu</name></author><author><name sortKey="Yang, H" uniqKey="Yang H">H Yang</name></author><author><name sortKey="Xue, F" uniqKey="Xue F">F Xue</name></author><author><name sortKey="Wu, Z" uniqKey="Wu Z">Z Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anand, K" uniqKey="Anand K">K Anand</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J Ziebuhr</name></author><author><name sortKey="Wadhwani, P" uniqKey="Wadhwani P">P Wadhwani</name></author><author><name sortKey="Mesters, Jr" uniqKey="Mesters J">JR Mesters</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R Hilgenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, Q" uniqKey="Zhao Q">Q Zhao</name></author><author><name sortKey="Li, S" uniqKey="Li S">S Li</name></author><author><name sortKey="Xue, F" uniqKey="Xue F">F Xue</name></author><author><name sortKey="Zou, Y" uniqKey="Zou Y">Y Zou</name></author><author><name sortKey="Chen, C" uniqKey="Chen C">C Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jenkins, Gm" uniqKey="Jenkins G">GM Jenkins</name></author><author><name sortKey="Rambaut, A" uniqKey="Rambaut A">A Rambaut</name></author><author><name sortKey="Pybus, Og" uniqKey="Pybus O">OG Pybus</name></author><author><name sortKey="Holmes, Ec" uniqKey="Holmes E">EC Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, Mm" uniqKey="Lai M">MM Lai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pasternak, Ao" uniqKey="Pasternak A">AO Pasternak</name></author><author><name sortKey="Spaan, Wj" uniqKey="Spaan W">WJ Spaan</name></author><author><name sortKey="Snijder, Ej" uniqKey="Snijder E">EJ Snijder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Duffy, S" uniqKey="Duffy S">S Duffy</name></author><author><name sortKey="Shackelton, La" uniqKey="Shackelton L">LA Shackelton</name></author><author><name sortKey="Holmes, Ec" uniqKey="Holmes E">EC Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, L" uniqKey="Zhu L">L Zhu</name></author><author><name sortKey="George, S" uniqKey="George S">S George</name></author><author><name sortKey="Schmidt, Mf" uniqKey="Schmidt M">MF Schmidt</name></author><author><name sortKey="Al Gharabli, Si" uniqKey="Al Gharabli S">SI Al-Gharabli</name></author><author><name sortKey="Rademann, J" uniqKey="Rademann J">J Rademann</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22073294</article-id><article-id pub-id-type="pmc">3206940</article-id><article-id pub-id-type="publisher-id">PONE-D-11-15731</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0027228</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Enzymes</subject><subj-group><subject>Enzyme Kinetics</subject></subj-group></subj-group></subj-group><subj-group><subject>Microbiology</subject><subj-group><subject>Virology</subject><subj-group><subject>Viral Enzymes</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Infectious Diseases</subject><subj-group><subject>Viral Diseases</subject><subj-group><subject>SARS</subject></subj-group></subj-group></subj-group><subj-group><subject>Pulmonology</subject><subj-group><subject>Respiratory Infections</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses</article-title><alt-title alt-title-type="running-head">Substrate Specificities of 3C-Like Proteases</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Chuck</surname><given-names>Chi-Pang</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chow</surname><given-names>Hak-Fun</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wan</surname><given-names>David Chi-Cheong</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wong</surname><given-names>Kam-Bo</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Department of Chemistry, The Chinese University of Hong Kong, Hong Kong, China</addr-line></aff><aff id="aff3"><label>3</label><addr-line>School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Poon</surname><given-names>Leo L. M.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1">University of Hong Kong, Hong Kong</aff><author-notes><corresp id="cor1">* E-mail: <email>kbwong@cuhk.edu.hk</email></corresp><fn fn-type="con"><p>Conceived and designed the experiments: C-PC DC-CW K-BW. Performed the experiments: C-PC. Analyzed the data: C-PC K-BW. Contributed reagents/materials/analysis tools: H-FC DC-CW. Wrote the paper: C-PC K-BW.</p></fn></author-notes><pub-date pub-type="collection"><year>2011</year></pub-date><pub-date pub-type="epub"><day>2</day><month>11</month><year>2011</year></pub-date><volume>6</volume><issue>11</issue><elocation-id>e27228</elocation-id><history><date date-type="received"><day>10</day><month>8</month><year>2011</year></date><date date-type="accepted"><day>12</day><month>10</month><year>2011</year></date></history><permissions><copyright-statement>Chuck et al.</copyright-statement><copyright-year>2011</copyright-year><license xlink:href="https://creativecommons.org/publicdomain/zero/1.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.</license-p></license></permissions><abstract><sec><title>Background</title><p>Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CL<sup>pro</sup>), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection.</p></sec><sec><title>Methodology/Principal Findings</title><p>Here, we profiled the substrate specificities of 3CL<sup>pro</sup> from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS-CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 19×8 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CL<sup>pro</sup> prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CL<sup>pro</sup> from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CL<sup>pro</sup> prefers P4-Pro and SARS-CoV 3CL<sup>pro</sup> prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences ‘VARLQ↓SGF’ that can be cleaved efficiently by all 3CL<sup>pro</sup> with relative activity of 1.7 to 3.2, and ‘VPRLQ↓SGF’ that can be cleaved specifically by IBV 3CL<sup>pro</sup> with relative activity of 4.3.</p></sec><sec><title>Conclusions/Significance</title><p>The comprehensive substrate specificities of 3CL<sup>pro</sup> from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases.</p></sec></abstract><counts><page-count count="6"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001373 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 001373 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Pmc
|étape= Curation
|type= RBID
|clé= PMC:3206940
|texte= Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:22073294" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |