CovidV2, Pmc, Corpus, bibRecord, 000449

Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain

Identifieur interne : 000449 ( Pmc/Corpus ); précédent : 000448; suivant : 000450

Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain

Auteurs : Kanchan Anand ; Gottfried J. Palm ; Jeroen R. Mesters ; Stuart G. Siddell ; John Ziebuhr ; Rolf Hilgenfeld

Source :

The EMBO Journal [ 0261-4189 ] ; 2002.

RBID : PMC:126080

Abstract

The key enzyme in coronavirus polyprotein processing is the viral main proteinase, M^pro, a protein with extremely low sequence similarity to other viral and cellular proteinases. Here, the crystal structure of the 33.1 kDa transmissible gastroenteritis (corona)virus M^pro is reported. The structure was refined to 1.96 Å resolution and revealed three dimers in the asymmetric unit. The mutual arrangement of the protomers in each of the dimers suggests that M^pro self-processing occurs in trans. The active site, comprised of Cys144 and His41, is part of a chymotrypsin-like fold that is connected by a 16 residue loop to an extra domain featuring a novel α-helical fold. Molecular modelling and mutagenesis data implicate the loop in substrate binding and elucidate S1 and S2 subsites suitable to accommodate the side chains of the P1 glutamine and P2 leucine residues of M^pro substrates. Interactions involving the N-terminus and the α-helical domain stabilize the loop in the orientation required for trans-cleavage activity. The study illustrates that RNA viruses have evolved unprecedented variations of the classical chymotrypsin fold.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC126080

DOI: 10.1093/emboj/cdf327
PubMed: 12093723
PubMed Central: 126080

Links to Exploration step

PMC:126080

Le document en format XML

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<author><name sortKey="Anand, Kanchan" sort="Anand, Kanchan" uniqKey="Anand K" first="Kanchan" last="Anand">Kanchan Anand</name>
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<author><name sortKey="Palm, Gottfried J" sort="Palm, Gottfried J" uniqKey="Palm G" first="Gottfried J." last="Palm">Gottfried J. Palm</name>
</author>
<author><name sortKey="Mesters, Jeroen R" sort="Mesters, Jeroen R" uniqKey="Mesters J" first="Jeroen R." last="Mesters">Jeroen R. Mesters</name>
</author>
<author><name sortKey="Siddell, Stuart G" sort="Siddell, Stuart G" uniqKey="Siddell S" first="Stuart G." last="Siddell">Stuart G. Siddell</name>
<affiliation><nlm:aff id="N0x99a9038.0x98cb100"></nlm:aff>
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<author><name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name>
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<author><name sortKey="Hilgenfeld, Rolf" sort="Hilgenfeld, Rolf" uniqKey="Hilgenfeld R" first="Rolf" last="Hilgenfeld">Rolf Hilgenfeld</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain</title>
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<author><name sortKey="Palm, Gottfried J" sort="Palm, Gottfried J" uniqKey="Palm G" first="Gottfried J." last="Palm">Gottfried J. Palm</name>
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<author><name sortKey="Mesters, Jeroen R" sort="Mesters, Jeroen R" uniqKey="Mesters J" first="Jeroen R." last="Mesters">Jeroen R. Mesters</name>
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<author><name sortKey="Siddell, Stuart G" sort="Siddell, Stuart G" uniqKey="Siddell S" first="Stuart G." last="Siddell">Stuart G. Siddell</name>
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<series><title level="j">The EMBO Journal</title>
<idno type="ISSN">0261-4189</idno>
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<front><div type="abstract" xml:lang="en"><p>The key enzyme in coronavirus polyprotein processing is the viral main proteinase, M<sup>pro</sup>
, a protein with extremely low sequence similarity to other viral and cellular proteinases. Here, the crystal structure of the 33.1 kDa transmissible gastroenteritis (corona)virus M<sup>pro</sup>
 is reported. The structure was refined to 1.96 Å resolution and revealed three dimers in the asymmetric unit. The mutual arrangement of the protomers in each of the dimers suggests that M<sup>pro</sup>
 self-processing occurs <italic>in trans</italic>
. The active site, comprised of Cys144 and His41, is part of a chymotrypsin-like fold that is connected by a 16 residue loop to an extra domain featuring a novel α-helical fold. Molecular modelling and mutagenesis data implicate the loop in substrate binding and elucidate S1 and S2 subsites suitable to accommodate the side chains of the P1 glutamine and P2 leucine residues of M<sup>pro</sup>
 substrates. Interactions involving the N-terminus and the α-helical domain stabilize the loop in the orientation required for <italic>trans</italic>
-cleavage activity. The study illustrates that RNA viruses have evolved unprecedented variations of the classical chymotrypsin fold.</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">EMBO J</journal-id>
<journal-title>The EMBO Journal</journal-title>
<issn pub-type="ppub">0261-4189</issn>
<issn pub-type="epub">1460-2075</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
<publisher-loc>Oxford, UK</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">12093723</article-id>
<article-id pub-id-type="pmc">126080</article-id>
<article-id pub-id-type="publisher-id">cdf327</article-id>
<article-id pub-id-type="doi">10.1093/emboj/cdf327</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Anand</surname>
<given-names>Kanchan</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Palm</surname>
<given-names>Gottfried J.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Mesters</surname>
<given-names>Jeroen R.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Siddell</surname>
<given-names>Stuart G.</given-names>
</name>
<xref ref-type="aff" rid="N0x99a9038.0x98cb100">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ziebuhr</surname>
<given-names>John</given-names>
</name>
<xref ref-type="aff" rid="N0x99a9038.0x98cb100">1</xref>
<xref ref-type="aff" rid="N0x99a9038.0x98cb100">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hilgenfeld</surname>
<given-names>Rolf</given-names>
</name>
<xref ref-type="aff" rid="N0x99a9038.0x98cb100">2</xref>
</contrib>
</contrib-group>
<aff id="N0x99a9038.0x98cb100">Department of Structural Biology and Crystallography, Institute of Molecular Biotechnology, D-07745 Jena and<label>1</label>
Institute of Virology and Immunology, University of Würzburg, D-97078 Würzburg, Germany<label>2</label>
Corresponding authors e-mail: hilgenfd@imb-jena.de or ziebuhr@vim.uni-wuerzburg.de</aff>
<pub-date pub-type="ppub"><day>1</day>
<month>7</month>
<year>2002</year>
</pub-date>
<volume>21</volume>
<issue>13</issue>
<fpage>3213</fpage>
<lpage>3224</lpage>
<ext-link ext-link-type="uri" xlink:href="http://www.emboj.oupjournals.org/content/vol21/issue13/"></ext-link>
<history><date date-type="received"><day>10</day>
<month>1</month>
<year>2002</year>
</date>
<date date-type="rev-recd"><day>9</day>
<month>4</month>
<year>2002</year>
</date>
<date date-type="accepted"><day>3</day>
<month>5</month>
<year>2002</year>
</date>
</history>
<copyright-statement>Copyright © 2002 European Molecular Biology Organization</copyright-statement>
<copyright-year>2002</copyright-year>
<abstract><p>The key enzyme in coronavirus polyprotein processing is the viral main proteinase, M<sup>pro</sup>
, a protein with extremely low sequence similarity to other viral and cellular proteinases. Here, the crystal structure of the 33.1 kDa transmissible gastroenteritis (corona)virus M<sup>pro</sup>
 is reported. The structure was refined to 1.96 Å resolution and revealed three dimers in the asymmetric unit. The mutual arrangement of the protomers in each of the dimers suggests that M<sup>pro</sup>
 self-processing occurs <italic>in trans</italic>
. The active site, comprised of Cys144 and His41, is part of a chymotrypsin-like fold that is connected by a 16 residue loop to an extra domain featuring a novel α-helical fold. Molecular modelling and mutagenesis data implicate the loop in substrate binding and elucidate S1 and S2 subsites suitable to accommodate the side chains of the P1 glutamine and P2 leucine residues of M<sup>pro</sup>
 substrates. Interactions involving the N-terminus and the α-helical domain stabilize the loop in the orientation required for <italic>trans</italic>
-cleavage activity. The study illustrates that RNA viruses have evolved unprecedented variations of the classical chymotrypsin fold.</p>
</abstract>
<kwd-group><kwd>3C-like/catalytic dyad/coronavirus/proteinase/X-ray crystallography</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain

Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain

Source :

Abstract

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