Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure.
Identifieur interne : 002982 ( Main/Exploration ); précédent : 002981; suivant : 002983Two adjacent mutations on the dimer interface of SARS coronavirus 3C-like protease cause different conformational changes in crystal structure.
Auteurs : Tiancen Hu [République populaire de Chine] ; Yu Zhang ; Lianwei Li ; Kuifeng Wang ; Shuai Chen ; Jing Chen ; Jianping Ding ; Hualiang Jiang ; Xu ShenSource :
- Virology [ 1096-0341 ] ; 2009.
Descripteurs français
- KwdFr :
- Cysteine endopeptidases (), Cysteine endopeptidases (génétique), Cysteine endopeptidases (isolement et purification), Cysteine endopeptidases (métabolisme), Dimérisation, Modèles moléculaires, Mutation, Protéines virales (), Protéines virales (génétique), Protéines virales (isolement et purification), Protéines virales (métabolisme), Relation structure-activité, Structure tertiaire des protéines (génétique), Virus du SRAS (enzymologie), Virus du SRAS (génétique).
- MESH :
- enzymologie : Virus du SRAS.
- génétique : Cysteine endopeptidases, Protéines virales, Structure tertiaire des protéines, Virus du SRAS.
- isolement et purification : Cysteine endopeptidases, Protéines virales.
- métabolisme : Cysteine endopeptidases, Protéines virales.
- Cysteine endopeptidases, Dimérisation, Modèles moléculaires, Mutation, Protéines virales, Relation structure-activité.
English descriptors
- KwdEn :
- Cysteine Endopeptidases (chemistry), Cysteine Endopeptidases (genetics), Cysteine Endopeptidases (isolation & purification), Cysteine Endopeptidases (metabolism), Dimerization, Models, Molecular, Mutation, Protein Structure, Tertiary (genetics), SARS Virus (enzymology), SARS Virus (genetics), Structure-Activity Relationship, Viral Proteins (chemistry), Viral Proteins (genetics), Viral Proteins (isolation & purification), Viral Proteins (metabolism).
- MESH :
- chemical , chemistry : Cysteine Endopeptidases, Viral Proteins.
- chemical , genetics : Cysteine Endopeptidases, Viral Proteins.
- chemical , isolation & purification : Cysteine Endopeptidases, Viral Proteins.
- chemical , metabolism : Cysteine Endopeptidases, Viral Proteins.
- enzymology : SARS Virus.
- genetics : Protein Structure, Tertiary, SARS Virus.
- Dimerization, Models, Molecular, Mutation, Structure-Activity Relationship.
Abstract
The 3C-like protease of SARS coronavirus (SARS-CoV 3CL(pro)) is vital for SARS-CoV replication and is a promising drug target. It has been extensively proved that only the dimeric enzyme is active. Here we discovered that two adjacent mutations (Ser139_Ala and Phe140_Ala) on the dimer interface resulted in completely different crystal structures of the enzyme, demonstrating the distinct roles of these two residues in maintaining the active conformation of SARS-CoV 3CL(pro). S139A is a monomer that is structurally similar to the two reported monomers G11A and R298A. However, this mutant still retains a small fraction of dimer in solution, which might account for its remaining activity. F140A is a dimer with the most collapsed active pocket discovered so far, well-reflecting the stabilizing role of this residue. Moreover, a plausible dimerization mechanism was also deduced from structural analysis. Our work is expected to provide insight on the dimerization-function relationship of SARS-CoV 3CL(pro).
DOI: 10.1016/j.virol.2009.03.034
PubMed: 19409595
Affiliations:
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Le document en format XML
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uniqKey="Zhang Y" first="Yu" last="Zhang">Yu Zhang</name></author><author><name sortKey="Li, Lianwei" sort="Li, Lianwei" uniqKey="Li L" first="Lianwei" last="Li">Lianwei Li</name></author><author><name sortKey="Wang, Kuifeng" sort="Wang, Kuifeng" uniqKey="Wang K" first="Kuifeng" last="Wang">Kuifeng Wang</name></author><author><name sortKey="Chen, Shuai" sort="Chen, Shuai" uniqKey="Chen S" first="Shuai" last="Chen">Shuai Chen</name></author><author><name sortKey="Chen, Jing" sort="Chen, Jing" uniqKey="Chen J" first="Jing" last="Chen">Jing Chen</name></author><author><name sortKey="Ding, Jianping" sort="Ding, Jianping" uniqKey="Ding J" first="Jianping" last="Ding">Jianping Ding</name></author><author><name sortKey="Jiang, Hualiang" sort="Jiang, Hualiang" uniqKey="Jiang H" first="Hualiang" last="Jiang">Hualiang Jiang</name></author><author><name sortKey="Shen, Xu" sort="Shen, Xu" uniqKey="Shen X" first="Xu" last="Shen">Xu Shen</name></author></titleStmt><publicationStmt><idno 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Zhang</name></author><author><name sortKey="Li, Lianwei" sort="Li, Lianwei" uniqKey="Li L" first="Lianwei" last="Li">Lianwei Li</name></author><author><name sortKey="Wang, Kuifeng" sort="Wang, Kuifeng" uniqKey="Wang K" first="Kuifeng" last="Wang">Kuifeng Wang</name></author><author><name sortKey="Chen, Shuai" sort="Chen, Shuai" uniqKey="Chen S" first="Shuai" last="Chen">Shuai Chen</name></author><author><name sortKey="Chen, Jing" sort="Chen, Jing" uniqKey="Chen J" first="Jing" last="Chen">Jing Chen</name></author><author><name sortKey="Ding, Jianping" sort="Ding, Jianping" uniqKey="Ding J" first="Jianping" last="Ding">Jianping Ding</name></author><author><name sortKey="Jiang, Hualiang" sort="Jiang, Hualiang" uniqKey="Jiang H" first="Hualiang" last="Jiang">Hualiang Jiang</name></author><author><name sortKey="Shen, Xu" sort="Shen, Xu" uniqKey="Shen X" first="Xu" last="Shen">Xu Shen</name></author></analytic><series><title level="j">Virology</title><idno 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scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Protein Structure, Tertiary</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Protéines virales</term><term>Structure tertiaire des protéines</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Protéines virales</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Dimerization</term><term>Models, Molecular</term><term>Mutation</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Dimérisation</term><term>Modèles moléculaires</term><term>Mutation</term><term>Protéines virales</term><term>Relation structure-activité</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The 3C-like protease of SARS coronavirus (SARS-CoV 3CL(pro)) is vital for SARS-CoV replication and is a promising drug target. It has been extensively proved that only the dimeric enzyme is active. Here we discovered that two adjacent mutations (Ser139_Ala and Phe140_Ala) on the dimer interface resulted in completely different crystal structures of the enzyme, demonstrating the distinct roles of these two residues in maintaining the active conformation of SARS-CoV 3CL(pro). S139A is a monomer that is structurally similar to the two reported monomers G11A and R298A. However, this mutant still retains a small fraction of dimer in solution, which might account for its remaining activity. F140A is a dimer with the most collapsed active pocket discovered so far, well-reflecting the stabilizing role of this residue. Moreover, a plausible dimerization mechanism was also deduced from structural analysis. Our work is expected to provide insight on the dimerization-function relationship of SARS-CoV 3CL(pro).</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Chen, Jing" sort="Chen, Jing" uniqKey="Chen J" first="Jing" last="Chen">Jing Chen</name><name sortKey="Chen, Shuai" sort="Chen, Shuai" uniqKey="Chen S" first="Shuai" last="Chen">Shuai Chen</name><name sortKey="Ding, Jianping" sort="Ding, Jianping" uniqKey="Ding J" first="Jianping" last="Ding">Jianping Ding</name><name sortKey="Jiang, Hualiang" sort="Jiang, Hualiang" uniqKey="Jiang H" first="Hualiang" last="Jiang">Hualiang Jiang</name><name sortKey="Li, Lianwei" sort="Li, Lianwei" uniqKey="Li L" first="Lianwei" last="Li">Lianwei Li</name><name sortKey="Shen, Xu" sort="Shen, Xu" uniqKey="Shen X" first="Xu" last="Shen">Xu Shen</name><name sortKey="Wang, Kuifeng" sort="Wang, Kuifeng" uniqKey="Wang K" first="Kuifeng" last="Wang">Kuifeng Wang</name><name sortKey="Zhang, Yu" sort="Zhang, Yu" uniqKey="Zhang Y" first="Yu" last="Zhang">Yu Zhang</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Hu, Tiancen" sort="Hu, Tiancen" uniqKey="Hu T" first="Tiancen" last="Hu">Tiancen Hu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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