Papain-Like Protease 2 (PLP2) from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV): Expression, Purification, Characterization, and Inhibition†
Identifieur interne : 001A44 ( Istex/Curation ); précédent : 001A43; suivant : 001A45Papain-Like Protease 2 (PLP2) from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV): Expression, Purification, Characterization, and Inhibition†
Auteurs : Yu-San Han [République populaire de Chine] ; Gu-Gang Chang [République populaire de Chine] ; Chiun-Gung Juo [République populaire de Chine] ; Hong-Jen Lee [République populaire de Chine] ; Shiou-Hwei Yeh [République populaire de Chine] ; John Tsu-An Hsu [République populaire de Chine] ; Xin Chen [République populaire de Chine, Taïwan]Source :
- Biochemistry [ 0006-2960 ] ; 2005.
Abstract
Viral proteases are essential for pathogenesis and virulence of severe acute respiratory syndrome coronavirus (SARS-CoV). Little information is available on SARS-CoV papain-like protease 2 (PLP2), and development of inhibitors against PLP2 is attractive for antiviral therapy. Here, we report the characterization of SARS-CoV PLP2 (from residues 1414 to 1858) purified from baculovirus-infected insect cells. We demonstrate that SARS-CoV PLP2 by itself differentially cleaves between the amino acids Gly180 and Ala181, Gly818 and Ala819, and Gly2740 and Lys2741 of the viral polypeptide pp1a, as determined by reversed-phase high-performance liquid chromatography analysis coupled with mass spectrometry. This protease is especially selective for the P1, P4, and P6 sites of the substrate. The study demonstrates, for the first time among coronaviral PLPs, that the reaction mechanism of SARS-CoV PLP2 is characteristic of papain and compatible with the involvement of the catalytic dyad (Cys)-S-/(His)-Im+H ion pair. With a fluorogenic inhibitor-screening platform, we show that zinc ion and its conjugates potently inhibit the enzymatic activity of SARS-CoV PLP2. In addition, we provided evidence for evolutionary reclassification of SARS-CoV. The results provide important insights into the biochemical properties of the coronaviral PLP family and a promising therapeutic way to fight SARS-CoV.
Url:
DOI: 10.1021/bi0504761
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Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350, Republic of China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 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code="subField">Institutes.</wicri:noCountry></affiliation><affiliation wicri:level="1"><mods:affiliation> To whom correspondence should be addressed: Division of Biotechnology and Pharmaceutical Research, National Health ResearchInstitutes, Miaoli County, Taiwan 350, Republic of China. Telephone: 88637 246166 ext. 35718. Fax: 88637 586456. E-mail: xchen@nhri.org.tw.</mods:affiliation><country wicri:rule="url">Taïwan</country><wicri:regionArea> To whom correspondence should be addressed: Division of Biotechnology and Pharmaceutical Research, National Health ResearchInstitutes, Miaoli County, Taiwan 350</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:4F0E4AFE461DA666EE29EB3709FAED6D24EE468B</idno><date when="2005" year="2005">2005</date><idno type="doi">10.1021/bi0504761</idno><idno type="url">https://api.istex.fr/ark:/67375/TPS-D5BW2ZKB-0/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001A44</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001A44</idno><idno type="wicri:Area/Istex/Curation">001A44</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Papain-Like Protease 2 (PLP2) from Severe Acute Respiratory Syndrome
Coronavirus (SARS-CoV): Expression, Purification, Characterization, and
Inhibition<ref type="bib" target="#bi0504761AF2">†</ref></title><author><name sortKey="Han, Yu San" sort="Han, Yu San" uniqKey="Han Y" first="Yu-San" last="Han">Yu-San Han</name><affiliation wicri:level="1"><mods:affiliation>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350, Republic of China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350</wicri:regionArea></affiliation><affiliation><mods:affiliation> Division of Biotechnology and Pharmaceutical Research, NationalHealth Research Institutes.</mods:affiliation></affiliation></author><author><name sortKey="Chang, Gu Gang" sort="Chang, Gu Gang" uniqKey="Chang G" first="Gu-Gang" last="Chang">Gu-Gang Chang</name><affiliation wicri:level="1"><mods:affiliation>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350, Republic of China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350</wicri:regionArea></affiliation><affiliation><mods:affiliation> National Yang-Ming University.</mods:affiliation></affiliation></author><author><name sortKey="Juo, Chiun Gung" sort="Juo, Chiun Gung" uniqKey="Juo C" first="Chiun-Gung" last="Juo">Chiun-Gung Juo</name><affiliation wicri:level="1"><mods:affiliation>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350, Republic of China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350</wicri:regionArea></affiliation><affiliation><mods:affiliation> Academia Sinica.</mods:affiliation></affiliation></author><author><name sortKey="Lee, Hong Jen" sort="Lee, Hong Jen" uniqKey="Lee H" first="Hong-Jen" last="Lee">Hong-Jen Lee</name><affiliation wicri:level="1"><mods:affiliation>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350, Republic of China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350</wicri:regionArea></affiliation><affiliation><mods:affiliation> Division of Biotechnology and Pharmaceutical Research, NationalHealth Research Institutes.</mods:affiliation></affiliation></author><author><name sortKey="Yeh, Shiou Hwei" sort="Yeh, Shiou Hwei" uniqKey="Yeh S" first="Shiou-Hwei" last="Yeh">Shiou-Hwei Yeh</name><affiliation wicri:level="1"><mods:affiliation>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350, Republic of China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350</wicri:regionArea></affiliation><affiliation><mods:affiliation> Division of Molecular and Genomic Medicine, National HealthResearch Institutes.</mods:affiliation></affiliation></author><author><name sortKey="Hsu, John Tsu An" sort="Hsu, John Tsu An" uniqKey="Hsu J" first="John Tsu-An" last="Hsu">John Tsu-An Hsu</name><affiliation wicri:level="1"><mods:affiliation>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350, Republic of China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350</wicri:regionArea></affiliation><affiliation><mods:affiliation> Division of Biotechnology and Pharmaceutical Research, NationalHealth Research Institutes.</mods:affiliation></affiliation></author><author><name sortKey="Chen, Xin" sort="Chen, Xin" uniqKey="Chen X" first="Xin" last="Chen">Xin Chen</name><affiliation wicri:level="1"><mods:affiliation>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350, Republic of China</mods:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 350,Republic of China, Faculty of Life Science, National Yang-Ming University, Taipei, Taiwan 112, Republic of China, Institute ofBiomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China, Division of Molecular and Genomic Medicine,National Health Research Institutes, Miaoli County, Taiwan 350</wicri:regionArea></affiliation><affiliation><mods:affiliation> Division of Biotechnology and Pharmaceutical Research, NationalHealth Research Institutes.</mods:affiliation></affiliation><affiliation wicri:level="1"><mods:affiliation> To whom correspondence should be addressed: Division of Biotechnology and Pharmaceutical Research, National Health ResearchInstitutes, Miaoli County, Taiwan 350, Republic of China. Telephone: 88637 246166 ext. 35718. Fax: 88637 586456. E-mail: xchen@nhri.org.tw.</mods:affiliation><country wicri:rule="url">Taïwan</country><wicri:regionArea> To whom correspondence should be addressed: Division of Biotechnology and Pharmaceutical Research, National Health ResearchInstitutes, Miaoli County, Taiwan 350</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Biochemistry</title><title level="j" type="abbrev">Biochemistry</title><idno type="ISSN">0006-2960</idno><idno type="eISSN">1520-4995</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published">2005</date><date type="published">2005</date><biblScope unit="vol">44</biblScope><biblScope unit="issue">30</biblScope><biblScope unit="page" from="10349">10349</biblScope><biblScope unit="page" to="10359">10359</biblScope></imprint><idno type="ISSN">0006-2960</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-2960</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Viral proteases are essential for pathogenesis and virulence of severe acute respiratory syndrome coronavirus (SARS-CoV). Little information is available on SARS-CoV papain-like protease 2 (PLP2), and development of inhibitors against PLP2 is attractive for antiviral therapy. Here, we report the characterization of SARS-CoV PLP2 (from residues 1414 to 1858) purified from baculovirus-infected insect cells. We demonstrate that SARS-CoV PLP2 by itself differentially cleaves between the amino acids Gly180 and Ala181, Gly818 and Ala819, and Gly2740 and Lys2741 of the viral polypeptide pp1a, as determined by reversed-phase high-performance liquid chromatography analysis coupled with mass spectrometry. This protease is especially selective for the P1, P4, and P6 sites of the substrate. The study demonstrates, for the first time among coronaviral PLPs, that the reaction mechanism of SARS-CoV PLP2 is characteristic of papain and compatible with the involvement of the catalytic dyad (Cys)-S-/(His)-Im+H ion pair. With a fluorogenic inhibitor-screening platform, we show that zinc ion and its conjugates potently inhibit the enzymatic activity of SARS-CoV PLP2. In addition, we provided evidence for evolutionary reclassification of SARS-CoV. The results provide important insights into the biochemical properties of the coronaviral PLP family and a promising therapeutic way to fight SARS-CoV.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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