Insight into the activity of SARS main protease: Molecular dynamics study of dimeric and monomeric form of enzyme.
Identifieur interne : 001F96 ( PubMed/Corpus ); précédent : 001F95; suivant : 001F97Insight into the activity of SARS main protease: Molecular dynamics study of dimeric and monomeric form of enzyme.
Auteurs : Kewen Zheng ; Guozheng Ma ; Jinming Zhou ; Min Zen ; Wenna Zhao ; Yongjun Jiang ; Qingsen Yu ; Jialiang FengSource :
- Proteins [ 1097-0134 ] ; 2007.
English descriptors
- KwdEn :
- Catalytic Domain, Computer Simulation, Cysteine Endopeptidases (chemistry), Cysteine Endopeptidases (metabolism), Dimerization, Hydrogen Bonding, Hydrolysis, Models, Chemical, Models, Molecular, Protease Inhibitors (pharmacology), Protein Conformation, Protein Interaction Mapping, SARS Virus (enzymology), Structure-Activity Relationship, Substrate Specificity, Viral Proteins (chemistry), Viral Proteins (metabolism), Water.
- MESH :
- chemical , chemistry : Cysteine Endopeptidases, Viral Proteins.
- chemical , metabolism : Cysteine Endopeptidases, Viral Proteins.
- chemical , pharmacology : Protease Inhibitors.
- enzymology : SARS Virus.
- Catalytic Domain, Computer Simulation, Dimerization, Hydrogen Bonding, Hydrolysis, Models, Chemical, Models, Molecular, Protein Conformation, Protein Interaction Mapping, Structure-Activity Relationship, Substrate Specificity, Water.
Abstract
The phenomenon that SARS coronavirus main protease (SARS M(pro)) dimer is the main functional form has been confirmed by experiment. However, because of the absence of structural information of the monomer, the reasons for this remain unknown. To investigate it, two molecular dynamics (MD) simulations in water for dimer and monomer models have been carried out, using the crystal structure of protomer A of the dimer as the starting structure for the monomer. During the MD simulation of dimer, three interest phenomena of protomer A have been observed: (i) the distance between NE2 of His41 and SG of Cys145 averages 3.72 A, which agrees well with the experimental observations made by X-ray crystallography; (ii) His163 and Glu166 form the "tooth" conformational properties, resulting in the specificity for glutamine at substrate P1 site; and (iii) the substrate-binding pocket formed by loop 140-146 and loop 184-197 is large enough to accommodate the substrate analog. However, during the MD simulation of the monomer complex, the three structural characteristics are all absent, which results directly in the inactivation of the monomer. Throughout the MD simulation of the dimer, the N-terminus of protomer B forms stable hydrogen bonds with Phe140 and Glu166, through which His163, Glu166, and loop 140-146 are kept active form. Furthermore, a water-bridge has been found between the N-terminus of protomer B and Gly170, which stabilizes His172 and avoids it moving toward Tyr161 to disrupt the H-bond between Tyr161 and His163, stabilizing the conformation of His163. The interactions between the N-terminus and another monomer maintain the activity of dimer.
DOI: 10.1002/prot.21160
PubMed: 17083088
Links to Exploration step
pubmed:17083088Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Insight into the activity of SARS main protease: Molecular dynamics study of dimeric and monomeric form of enzyme.</title>
<author><name sortKey="Zheng, Kewen" sort="Zheng, Kewen" uniqKey="Zheng K" first="Kewen" last="Zheng">Kewen Zheng</name>
<affiliation><nlm:affiliation>Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200072, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ma, Guozheng" sort="Ma, Guozheng" uniqKey="Ma G" first="Guozheng" last="Ma">Guozheng Ma</name>
</author>
<author><name sortKey="Zhou, Jinming" sort="Zhou, Jinming" uniqKey="Zhou J" first="Jinming" last="Zhou">Jinming Zhou</name>
</author>
<author><name sortKey="Zen, Min" sort="Zen, Min" uniqKey="Zen M" first="Min" last="Zen">Min Zen</name>
</author>
<author><name sortKey="Zhao, Wenna" sort="Zhao, Wenna" uniqKey="Zhao W" first="Wenna" last="Zhao">Wenna Zhao</name>
</author>
<author><name sortKey="Jiang, Yongjun" sort="Jiang, Yongjun" uniqKey="Jiang Y" first="Yongjun" last="Jiang">Yongjun Jiang</name>
</author>
<author><name sortKey="Yu, Qingsen" sort="Yu, Qingsen" uniqKey="Yu Q" first="Qingsen" last="Yu">Qingsen Yu</name>
</author>
<author><name sortKey="Feng, Jialiang" sort="Feng, Jialiang" uniqKey="Feng J" first="Jialiang" last="Feng">Jialiang Feng</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2007">2007</date>
<idno type="RBID">pubmed:17083088</idno>
<idno type="pmid">17083088</idno>
<idno type="doi">10.1002/prot.21160</idno>
<idno type="wicri:Area/PubMed/Corpus">001F96</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001F96</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Insight into the activity of SARS main protease: Molecular dynamics study of dimeric and monomeric form of enzyme.</title>
<author><name sortKey="Zheng, Kewen" sort="Zheng, Kewen" uniqKey="Zheng K" first="Kewen" last="Zheng">Kewen Zheng</name>
<affiliation><nlm:affiliation>Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200072, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ma, Guozheng" sort="Ma, Guozheng" uniqKey="Ma G" first="Guozheng" last="Ma">Guozheng Ma</name>
</author>
<author><name sortKey="Zhou, Jinming" sort="Zhou, Jinming" uniqKey="Zhou J" first="Jinming" last="Zhou">Jinming Zhou</name>
</author>
<author><name sortKey="Zen, Min" sort="Zen, Min" uniqKey="Zen M" first="Min" last="Zen">Min Zen</name>
</author>
<author><name sortKey="Zhao, Wenna" sort="Zhao, Wenna" uniqKey="Zhao W" first="Wenna" last="Zhao">Wenna Zhao</name>
</author>
<author><name sortKey="Jiang, Yongjun" sort="Jiang, Yongjun" uniqKey="Jiang Y" first="Yongjun" last="Jiang">Yongjun Jiang</name>
</author>
<author><name sortKey="Yu, Qingsen" sort="Yu, Qingsen" uniqKey="Yu Q" first="Qingsen" last="Yu">Qingsen Yu</name>
</author>
<author><name sortKey="Feng, Jialiang" sort="Feng, Jialiang" uniqKey="Feng J" first="Jialiang" last="Feng">Jialiang Feng</name>
</author>
</analytic>
<series><title level="j">Proteins</title>
<idno type="eISSN">1097-0134</idno>
<imprint><date when="2007" type="published">2007</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Catalytic Domain</term>
<term>Computer Simulation</term>
<term>Cysteine Endopeptidases (chemistry)</term>
<term>Cysteine Endopeptidases (metabolism)</term>
<term>Dimerization</term>
<term>Hydrogen Bonding</term>
<term>Hydrolysis</term>
<term>Models, Chemical</term>
<term>Models, Molecular</term>
<term>Protease Inhibitors (pharmacology)</term>
<term>Protein Conformation</term>
<term>Protein Interaction Mapping</term>
<term>SARS Virus (enzymology)</term>
<term>Structure-Activity Relationship</term>
<term>Substrate Specificity</term>
<term>Viral Proteins (chemistry)</term>
<term>Viral Proteins (metabolism)</term>
<term>Water</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cysteine Endopeptidases</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine Endopeptidases</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Protease Inhibitors</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Catalytic Domain</term>
<term>Computer Simulation</term>
<term>Dimerization</term>
<term>Hydrogen Bonding</term>
<term>Hydrolysis</term>
<term>Models, Chemical</term>
<term>Models, Molecular</term>
<term>Protein Conformation</term>
<term>Protein Interaction Mapping</term>
<term>Structure-Activity Relationship</term>
<term>Substrate Specificity</term>
<term>Water</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The phenomenon that SARS coronavirus main protease (SARS M(pro)) dimer is the main functional form has been confirmed by experiment. However, because of the absence of structural information of the monomer, the reasons for this remain unknown. To investigate it, two molecular dynamics (MD) simulations in water for dimer and monomer models have been carried out, using the crystal structure of protomer A of the dimer as the starting structure for the monomer. During the MD simulation of dimer, three interest phenomena of protomer A have been observed: (i) the distance between NE2 of His41 and SG of Cys145 averages 3.72 A, which agrees well with the experimental observations made by X-ray crystallography; (ii) His163 and Glu166 form the "tooth" conformational properties, resulting in the specificity for glutamine at substrate P1 site; and (iii) the substrate-binding pocket formed by loop 140-146 and loop 184-197 is large enough to accommodate the substrate analog. However, during the MD simulation of the monomer complex, the three structural characteristics are all absent, which results directly in the inactivation of the monomer. Throughout the MD simulation of the dimer, the N-terminus of protomer B forms stable hydrogen bonds with Phe140 and Glu166, through which His163, Glu166, and loop 140-146 are kept active form. Furthermore, a water-bridge has been found between the N-terminus of protomer B and Gly170, which stabilizes His172 and avoids it moving toward Tyr161 to disrupt the H-bond between Tyr161 and His163, stabilizing the conformation of His163. The interactions between the N-terminus and another monomer maintain the activity of dimer.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17083088</PMID>
<DateCompleted><Year>2007</Year>
<Month>03</Month>
<Day>06</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>03</Month>
<Day>25</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1097-0134</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>66</Volume>
<Issue>2</Issue>
<PubDate><Year>2007</Year>
<Month>Feb</Month>
<Day>01</Day>
</PubDate>
</JournalIssue>
<Title>Proteins</Title>
<ISOAbbreviation>Proteins</ISOAbbreviation>
</Journal>
<ArticleTitle>Insight into the activity of SARS main protease: Molecular dynamics study of dimeric and monomeric form of enzyme.</ArticleTitle>
<Pagination><MedlinePgn>467-79</MedlinePgn>
</Pagination>
<Abstract><AbstractText>The phenomenon that SARS coronavirus main protease (SARS M(pro)) dimer is the main functional form has been confirmed by experiment. However, because of the absence of structural information of the monomer, the reasons for this remain unknown. To investigate it, two molecular dynamics (MD) simulations in water for dimer and monomer models have been carried out, using the crystal structure of protomer A of the dimer as the starting structure for the monomer. During the MD simulation of dimer, three interest phenomena of protomer A have been observed: (i) the distance between NE2 of His41 and SG of Cys145 averages 3.72 A, which agrees well with the experimental observations made by X-ray crystallography; (ii) His163 and Glu166 form the "tooth" conformational properties, resulting in the specificity for glutamine at substrate P1 site; and (iii) the substrate-binding pocket formed by loop 140-146 and loop 184-197 is large enough to accommodate the substrate analog. However, during the MD simulation of the monomer complex, the three structural characteristics are all absent, which results directly in the inactivation of the monomer. Throughout the MD simulation of the dimer, the N-terminus of protomer B forms stable hydrogen bonds with Phe140 and Glu166, through which His163, Glu166, and loop 140-146 are kept active form. Furthermore, a water-bridge has been found between the N-terminus of protomer B and Gly170, which stabilizes His172 and avoids it moving toward Tyr161 to disrupt the H-bond between Tyr161 and His163, stabilizing the conformation of His163. The interactions between the N-terminus and another monomer maintain the activity of dimer.</AbstractText>
<CopyrightInformation>Copyright 2006 Wiley-Liss, Inc.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zheng</LastName>
<ForeName>Kewen</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200072, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ma</LastName>
<ForeName>Guozheng</ForeName>
<Initials>G</Initials>
</Author>
<Author ValidYN="Y"><LastName>Zhou</LastName>
<ForeName>Jinming</ForeName>
<Initials>J</Initials>
</Author>
<Author ValidYN="Y"><LastName>Zen</LastName>
<ForeName>Min</ForeName>
<Initials>M</Initials>
</Author>
<Author ValidYN="Y"><LastName>Zhao</LastName>
<ForeName>Wenna</ForeName>
<Initials>W</Initials>
</Author>
<Author ValidYN="Y"><LastName>Jiang</LastName>
<ForeName>Yongjun</ForeName>
<Initials>Y</Initials>
</Author>
<Author ValidYN="Y"><LastName>Yu</LastName>
<ForeName>Qingsen</ForeName>
<Initials>Q</Initials>
</Author>
<Author ValidYN="Y"><LastName>Feng</LastName>
<ForeName>Jialiang</ForeName>
<Initials>J</Initials>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Proteins</MedlineTA>
<NlmUniqueID>8700181</NlmUniqueID>
<ISSNLinking>0887-3585</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011480">Protease Inhibitors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014764">Viral Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>059QF0KO0R</RegistryNumber>
<NameOfSubstance UI="D014867">Water</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber>
<NameOfSubstance UI="C099456">3C-like proteinase, Coronavirus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber>
<NameOfSubstance UI="D003546">Cysteine Endopeptidases</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D020134" MajorTopicYN="N">Catalytic Domain</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003198" MajorTopicYN="Y">Computer Simulation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003546" MajorTopicYN="N">Cysteine Endopeptidases</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019281" MajorTopicYN="N">Dimerization</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006860" MajorTopicYN="N">Hydrogen Bonding</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006868" MajorTopicYN="N">Hydrolysis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008956" MajorTopicYN="Y">Models, Chemical</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008958" MajorTopicYN="N">Models, Molecular</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011480" MajorTopicYN="N">Protease Inhibitors</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011487" MajorTopicYN="N">Protein Conformation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D025941" MajorTopicYN="N">Protein Interaction Mapping</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName>
<QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013379" MajorTopicYN="N">Substrate Specificity</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014867" MajorTopicYN="N">Water</DescriptorName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year>
<Month>11</Month>
<Day>4</Day>
<Hour>9</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2007</Year>
<Month>3</Month>
<Day>7</Day>
<Hour>9</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2006</Year>
<Month>11</Month>
<Day>4</Day>
<Hour>9</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">17083088</ArticleId>
<ArticleId IdType="doi">10.1002/prot.21160</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/PubMed/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001F96 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd -nk 001F96 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= PubMed |étape= Corpus |type= RBID |clé= pubmed:17083088 |texte= Insight into the activity of SARS main protease: Molecular dynamics study of dimeric and monomeric form of enzyme. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:17083088" \ | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |