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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor</title><author><name sortKey="Yang, Haitao" sort="Yang, Haitao" uniqKey="Yang H" first="Haitao" last="Yang">Haitao Yang</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Yang, Maojun" sort="Yang, Maojun" uniqKey="Yang M" first="Maojun" last="Yang">Maojun Yang</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Ding, Yi" sort="Ding, Yi" uniqKey="Ding Y" first="Yi" last="Ding">Yi Ding</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Liu, Yiwei" sort="Liu, Yiwei" uniqKey="Liu Y" first="Yiwei" last="Liu">Yiwei Liu</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Lou, Zhiyong" sort="Lou, Zhiyong" uniqKey="Lou Z" first="Zhiyong" last="Lou">Zhiyong Lou</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Zhou, Zhe" sort="Zhou, Zhe" uniqKey="Zhou Z" first="Zhe" last="Zhou">Zhe Zhou</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Sun, Lei" sort="Sun, Lei" uniqKey="Sun L" first="Lei" last="Sun">Lei Sun</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Mo, Lijuan" sort="Mo, Lijuan" uniqKey="Mo L" first="Lijuan" last="Mo">Lijuan Mo</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Ye, Sheng" sort="Ye, Sheng" uniqKey="Ye S" first="Sheng" last="Ye">Sheng Ye</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Pang, Hai" sort="Pang, Hai" uniqKey="Pang H" first="Hai" last="Pang">Hai Pang</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Anand, Kanchan" sort="Anand, Kanchan" uniqKey="Anand K" first="Kanchan" last="Anand">Kanchan Anand</name><affiliation><nlm:aff id="N0xa0e89f0.0x992f7d8">Institute of Biochemistry, University of Lübeck, 23538 Lübeck, Germany</nlm:aff></affiliation></author><author><name sortKey="Bartlam, Mark" sort="Bartlam, Mark" uniqKey="Bartlam M" first="Mark" last="Bartlam">Mark Bartlam</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Hilgenfeld, Rolf" sort="Hilgenfeld, Rolf" uniqKey="Hilgenfeld R" first="Rolf" last="Hilgenfeld">Rolf Hilgenfeld</name><affiliation><nlm:aff id="N0xa0e89f0.0x992f7d8">Institute of Biochemistry, University of Lübeck, 23538 Lübeck, Germany</nlm:aff></affiliation></author><author><name sortKey="Rao, Zihe" sort="Rao, Zihe" uniqKey="Rao Z" first="Zihe" last="Rao">Zihe Rao</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">14585926</idno><idno type="pmc">263746</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC263746</idno><idno type="RBID">PMC:263746</idno><idno type="doi">10.1073/pnas.1835675100</idno><date when="2003">2003</date><idno type="wicri:Area/Pmc/Corpus">000741</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000741</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor</title><author><name sortKey="Yang, Haitao" sort="Yang, Haitao" uniqKey="Yang H" first="Haitao" last="Yang">Haitao Yang</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Yang, Maojun" sort="Yang, Maojun" uniqKey="Yang M" first="Maojun" last="Yang">Maojun Yang</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Ding, Yi" sort="Ding, Yi" uniqKey="Ding Y" first="Yi" last="Ding">Yi Ding</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Liu, Yiwei" sort="Liu, Yiwei" uniqKey="Liu Y" first="Yiwei" last="Liu">Yiwei Liu</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Lou, Zhiyong" sort="Lou, Zhiyong" uniqKey="Lou Z" first="Zhiyong" last="Lou">Zhiyong Lou</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Zhou, Zhe" sort="Zhou, Zhe" uniqKey="Zhou Z" first="Zhe" last="Zhou">Zhe Zhou</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Sun, Lei" sort="Sun, Lei" uniqKey="Sun L" first="Lei" last="Sun">Lei Sun</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Mo, Lijuan" sort="Mo, Lijuan" uniqKey="Mo L" first="Lijuan" last="Mo">Lijuan Mo</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Ye, Sheng" sort="Ye, Sheng" uniqKey="Ye S" first="Sheng" last="Ye">Sheng Ye</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Pang, Hai" sort="Pang, Hai" uniqKey="Pang H" first="Hai" last="Pang">Hai Pang</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Anand, Kanchan" sort="Anand, Kanchan" uniqKey="Anand K" first="Kanchan" last="Anand">Kanchan Anand</name><affiliation><nlm:aff id="N0xa0e89f0.0x992f7d8">Institute of Biochemistry, University of Lübeck, 23538 Lübeck, Germany</nlm:aff></affiliation></author><author><name sortKey="Bartlam, Mark" sort="Bartlam, Mark" uniqKey="Bartlam M" first="Mark" last="Bartlam">Mark Bartlam</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author><author><name sortKey="Hilgenfeld, Rolf" sort="Hilgenfeld, Rolf" uniqKey="Hilgenfeld R" first="Rolf" last="Hilgenfeld">Rolf Hilgenfeld</name><affiliation><nlm:aff id="N0xa0e89f0.0x992f7d8">Institute of Biochemistry, University of Lübeck, 23538 Lübeck, Germany</nlm:aff></affiliation></author><author><name sortKey="Rao, Zihe" sort="Rao, Zihe" uniqKey="Rao Z" first="Zihe" last="Rao">Zihe Rao</name><affiliation><nlm:aff wicri:cut="; and" id="N0xa0e89f0.0x992f7d8">Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2003">2003</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>A newly identified severe acute respiratory syndrome coronavirus (SARS-CoV), is the etiological agent responsible for the outbreak of SARS. The SARS-CoV main protease, which is a 33.8-kDa protease (also called the 3C-like protease), plays a pivotal role in mediating viral replication and transcription functions through extensive proteolytic processing of two replicase polyproteins, pp1a (486 kDa) and pp1ab (790 kDa). Here, we report the crystal structures of the SARS-CoV main protease at different pH values and in complex with a specific inhibitor. The protease structure has a fold that can be described as an augmented serine-protease, but with a Cys-His at the active site. This series of crystal structures, which is the first, to our knowledge, of any protein from the SARS virus, reveal substantial pH-dependent conformational changes, and an unexpected mode of inhibitor binding, providing a structural basis for rational drug design.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="publisher-id">pnas</journal-id><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">14585926</article-id><article-id pub-id-type="pmc">263746</article-id><article-id pub-id-type="publisher-id">10013190</article-id><article-id pub-id-type="doi">10.1073/pnas.1835675100</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Biochemistry</subject></subj-group></subj-group></article-categories><title-group><article-title>The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Haitao</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Maojun</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Ding</surname><given-names>Yi</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Yiwei</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref></contrib><contrib contrib-type="author"><name><surname>Lou</surname><given-names>Zhiyong</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref></contrib><contrib contrib-type="author"><name><surname>Zhou</surname><given-names>Zhe</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Lei</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref></contrib><contrib contrib-type="author"><name><surname>Mo</surname><given-names>Lijuan</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref></contrib><contrib contrib-type="author"><name><surname>Ye</surname><given-names>Sheng</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref></contrib><contrib contrib-type="author"><name><surname>Pang</surname><given-names>Hai</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref></contrib><contrib contrib-type="author"><name><surname>Gao</surname><given-names>George F.</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref></contrib><contrib contrib-type="author"><name><surname>Anand</surname><given-names>Kanchan</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">‡</xref></contrib><contrib contrib-type="author"><name><surname>Bartlam</surname><given-names>Mark</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref></contrib><contrib contrib-type="author"><name><surname>Hilgenfeld</surname><given-names>Rolf</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">‡</xref></contrib><contrib contrib-type="author"><name><surname>Rao</surname><given-names>Zihe</given-names></name><xref ref-type="aff" rid="N0xa0e89f0.0x992f7d8">*</xref><xref ref-type="corresp" rid="cor1">§</xref></contrib></contrib-group><aff id="N0xa0e89f0.0x992f7d8"><label>*</label>Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, 100084 Beijing, China; and<label>‡</label>Institute of Biochemistry, University of Lübeck, 23538 Lübeck, Germany</aff><author-notes><fn id="cor1"><label>§</label><p> To whom correspondence should be addressed at: Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China. E-mail: <email>raozh@xtal.tsinghua.edu.cn</email>. </p></fn><fn id="fn1"><label>†</label><p>H.Y., M.Y., and Y.D. contributed equally to this work.</p></fn><fn><p>Communicated by Brian W. Matthews, University of Oregon, Eugene, OR, September 8, 2003</p></fn></author-notes><pub-date pub-type="ppub"><day>11</day><month>11</month><year>2003</year></pub-date><pub-date pub-type="epub"><day>29</day><month>10</month><year>2003</year></pub-date><volume>100</volume><issue>23</issue><fpage>13190</fpage><lpage>13195</lpage><history><date date-type="received"><day>25</day><month>8</month><year>2003</year></date></history><copyright-statement>Copyright © 2003, The National Academy of Sciences</copyright-statement><copyright-year>2003</copyright-year><abstract><p>A newly identified severe acute respiratory syndrome coronavirus (SARS-CoV), is the etiological agent responsible for the outbreak of SARS. The SARS-CoV main protease, which is a 33.8-kDa protease (also called the 3C-like protease), plays a pivotal role in mediating viral replication and transcription functions through extensive proteolytic processing of two replicase polyproteins, pp1a (486 kDa) and pp1ab (790 kDa). Here, we report the crystal structures of the SARS-CoV main protease at different pH values and in complex with a specific inhibitor. The protease structure has a fold that can be described as an augmented serine-protease, but with a Cys-His at the active site. This series of crystal structures, which is the first, to our knowledge, of any protein from the SARS virus, reveal substantial pH-dependent conformational changes, and an unexpected mode of inhibitor binding, providing a structural basis for rational drug design.</p></abstract></article-meta><notes><fn-group><fn><p>Abbreviations: SARS, severe acute respiratory syndrome; CoV, coronavirus; HcoV, human CoV; Mpro, main protease; TGEV, porcine transmissible gastroenteritis virus; PEG, polyethylene glycol; CMK, chloromethyl ketone; N-finger, N-terminal residues 1-7.</p></fn><fn><p>Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, <ext-link ext-link-type="uri" xlink:href="www.rcsb.org">www.rcsb.org</ext-link> [PDB ID codes 1UJ1, 1UK3, 1UK2 (SARS-CoV Mpro, apoenzyme at pH 6.0, 7.6, and 8.0, respectively), and 1UK4 (SARS-CoV Mpro in complex with the hexapeptidyl CMK inhibitor].</p></fn></fn-group></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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