Only one protomer is active in the dimer of SARS 3C-like proteinase.
Identifieur interne : 003D96 ( Main/Exploration ); précédent : 003D95; suivant : 003D97Only one protomer is active in the dimer of SARS 3C-like proteinase.
Auteurs : Hao Chen [République populaire de Chine] ; Ping Wei ; Changkang Huang ; Lei Tan ; Ying Liu ; Luhua LaiSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2006.
Descripteurs français
- KwdFr :
- Acide glutamique (), Catalyse, Cinétique, Colorimétrie, Conformation des protéines, Cristallisation, Cysteine endopeptidases (), Cysteine endopeptidases (physiologie), Dimérisation, Endopeptidases (), Liaison aux protéines, Liaison hydrogène, Protéines virales (), Protéines virales (physiologie), Sites de fixation, Sous-unités de protéines (), Spécificité du substrat, Structure tertiaire des protéines, Virus du SRAS (enzymologie).
- MESH :
- enzymologie : Virus du SRAS.
- physiologie : Cysteine endopeptidases, Protéines virales.
- Acide glutamique, Catalyse, Cinétique, Colorimétrie, Conformation des protéines, Cristallisation, Cysteine endopeptidases, Dimérisation, Endopeptidases, Liaison aux protéines, Liaison hydrogène, Protéines virales, Sites de fixation, Sous-unités de protéines, Spécificité du substrat, Structure tertiaire des protéines.
English descriptors
- KwdEn :
- Binding Sites, Catalysis, Colorimetry, Crystallization, Cysteine Endopeptidases (chemistry), Cysteine Endopeptidases (physiology), Dimerization, Endopeptidases (chemistry), Glutamic Acid (chemistry), Hydrogen Bonding, Kinetics, Protein Binding, Protein Conformation, Protein Structure, Tertiary, Protein Subunits (chemistry), SARS Virus (enzymology), Substrate Specificity, Viral Proteins (chemistry), Viral Proteins (physiology).
- MESH :
- chemical , chemistry : Cysteine Endopeptidases, Endopeptidases, Glutamic Acid, Protein Subunits, Viral Proteins.
- chemical , physiology : Cysteine Endopeptidases, Viral Proteins.
- enzymology : SARS Virus.
- Binding Sites, Catalysis, Colorimetry, Crystallization, Dimerization, Hydrogen Bonding, Kinetics, Protein Binding, Protein Conformation, Protein Structure, Tertiary, Substrate Specificity.
Abstract
The severe acute respiratory syndrome coronavirus 3C-like protease has been proposed to be a key target for structurally based drug design against SARS. The enzyme exists as a mixture of dimer and monomer, and only the dimer was considered to be active. In this report, we have investigated, using molecular dynamics simulation and mutational studies, the problems as to why only the dimer is active and whether both of the two protomers in the dimer are active. The molecular dynamics simulations show that the monomers are always inactive, that the two protomers in the dimer are asymmetric, and that only one protomer is active at a time. The enzyme activity of the hybrid severe acute respiratory syndrome coronavirus 3C-like protease of the wild-type protein and the inactive mutant proves that the dimerization is important for enzyme activity and only one active protomer in the dimer is enough for the catalysis. Our simulations also show that the right conformation for catalysis in one protomer can be induced upon dimer formation. These results suggest that the enzyme may follow the association, activation, catalysis, and dissociation mechanism for activity control.
DOI: 10.1074/jbc.M510745200
PubMed: 16565086
Affiliations:
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Le document en format XML
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Beijing 100871, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry, Peking University, Beijing 100871</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName><orgName type="university">Université de Pékin</orgName><placeName><settlement type="city">Pékin</settlement><region type="capitale">Pékin</region></placeName></affiliation></author><author><name sortKey="Wei, Ping" sort="Wei, Ping" uniqKey="Wei P" first="Ping" last="Wei">Ping Wei</name></author><author><name sortKey="Huang, Changkang" sort="Huang, Changkang" uniqKey="Huang C" first="Changkang" last="Huang">Changkang Huang</name></author><author><name sortKey="Tan, Lei" sort="Tan, Lei" uniqKey="Tan L" first="Lei" last="Tan">Lei Tan</name></author><author><name sortKey="Liu, Ying" sort="Liu, Ying" uniqKey="Liu Y" first="Ying" last="Liu">Ying Liu</name></author><author><name sortKey="Lai, Luhua" sort="Lai, Luhua" uniqKey="Lai L" first="Luhua" last="Lai">Luhua Lai</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="ISSN">0021-9258</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Binding Sites</term><term>Catalysis</term><term>Colorimetry</term><term>Crystallization</term><term>Cysteine Endopeptidases (chemistry)</term><term>Cysteine Endopeptidases (physiology)</term><term>Dimerization</term><term>Endopeptidases (chemistry)</term><term>Glutamic Acid (chemistry)</term><term>Hydrogen Bonding</term><term>Kinetics</term><term>Protein Binding</term><term>Protein Conformation</term><term>Protein Structure, Tertiary</term><term>Protein Subunits (chemistry)</term><term>SARS Virus (enzymology)</term><term>Substrate Specificity</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acide glutamique ()</term><term>Catalyse</term><term>Cinétique</term><term>Colorimétrie</term><term>Conformation des protéines</term><term>Cristallisation</term><term>Cysteine endopeptidases ()</term><term>Cysteine endopeptidases (physiologie)</term><term>Dimérisation</term><term>Endopeptidases ()</term><term>Liaison aux protéines</term><term>Liaison hydrogène</term><term>Protéines virales ()</term><term>Protéines virales (physiologie)</term><term>Sites de fixation</term><term>Sous-unités de protéines ()</term><term>Spécificité du substrat</term><term>Structure tertiaire des protéines</term><term>Virus du SRAS (enzymologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Endopeptidases</term><term>Glutamic Acid</term><term>Protein Subunits</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" 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="physiologie" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Protéines virales</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>Catalysis</term><term>Colorimetry</term><term>Crystallization</term><term>Dimerization</term><term>Hydrogen Bonding</term><term>Kinetics</term><term>Protein Binding</term><term>Protein Conformation</term><term>Protein Structure, Tertiary</term><term>Substrate Specificity</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Acide glutamique</term><term>Catalyse</term><term>Cinétique</term><term>Colorimétrie</term><term>Conformation des protéines</term><term>Cristallisation</term><term>Cysteine endopeptidases</term><term>Dimérisation</term><term>Endopeptidases</term><term>Liaison aux protéines</term><term>Liaison hydrogène</term><term>Protéines virales</term><term>Sites de fixation</term><term>Sous-unités de protéines</term><term>Spécificité du substrat</term><term>Structure tertiaire des protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The severe acute respiratory syndrome coronavirus 3C-like protease has been proposed to be a key target for structurally based drug design against SARS. The enzyme exists as a mixture of dimer and monomer, and only the dimer was considered to be active. In this report, we have investigated, using molecular dynamics simulation and mutational studies, the problems as to why only the dimer is active and whether both of the two protomers in the dimer are active. The molecular dynamics simulations show that the monomers are always inactive, that the two protomers in the dimer are asymmetric, and that only one protomer is active at a time. The enzyme activity of the hybrid severe acute respiratory syndrome coronavirus 3C-like protease of the wild-type protein and the inactive mutant proves that the dimerization is important for enzyme activity and only one active protomer in the dimer is enough for the catalysis. Our simulations also show that the right conformation for catalysis in one protomer can be induced upon dimer formation. These results suggest that the enzyme may follow the association, activation, catalysis, and dissociation mechanism for activity control.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Pékin</li></region><settlement><li>Pékin</li></settlement><orgName><li>Université de Pékin</li></orgName></list><tree><noCountry><name sortKey="Huang, Changkang" sort="Huang, Changkang" uniqKey="Huang C" first="Changkang" last="Huang">Changkang Huang</name><name sortKey="Lai, Luhua" sort="Lai, Luhua" uniqKey="Lai L" first="Luhua" last="Lai">Luhua Lai</name><name sortKey="Liu, Ying" sort="Liu, Ying" uniqKey="Liu Y" first="Ying" last="Liu">Ying Liu</name><name sortKey="Tan, Lei" sort="Tan, Lei" uniqKey="Tan L" first="Lei" last="Tan">Lei Tan</name><name sortKey="Wei, Ping" sort="Wei, Ping" uniqKey="Wei P" first="Ping" last="Wei">Ping Wei</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Chen, Hao" sort="Chen, Hao" uniqKey="Chen H" first="Hao" last="Chen">Hao Chen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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