Mechanism of the maturation process of SARS-CoV 3CL protease.
Identifieur interne : 004A43 ( Main/Merge ); précédent : 004A42; suivant : 004A44Mechanism of the maturation process of SARS-CoV 3CL protease.
Auteurs : Min-Feng Hsu ; Chih-Jung Kuo ; Kai-Ti Chang ; Hui-Chuan Chang ; Chia-Cheng Chou ; Tzu-Ping Ko ; Hui-Lin Shr ; Gu-Gang Chang ; Andrew H-J Wang ; Po-Huang LiangSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2005.
Descripteurs français
- KwdFr :
- Cristallographie aux rayons X, Cysteine endopeptidases, Endopeptidases (), Endopeptidases (génétique), Endopeptidases (métabolisme), Humains, Maturation post-traductionnelle des protéines, Modèles moléculaires, Protéines de fusion recombinantes (), Protéines de fusion recombinantes (génétique), Protéines de fusion recombinantes (métabolisme), Protéines virales (), Protéines virales (antagonistes et inhibiteurs), Protéines virales (génétique), Protéines virales (métabolisme), Sites de fixation, Structure moléculaire, Structure tertiaire des protéines, Virus du SRAS (enzymologie).
- MESH :
- antagonistes et inhibiteurs : Protéines virales.
- enzymologie : Virus du SRAS.
- génétique : Endopeptidases, Protéines de fusion recombinantes, Protéines virales.
- métabolisme : Endopeptidases, Protéines de fusion recombinantes, Protéines virales.
- Cristallographie aux rayons X, Cysteine endopeptidases, Endopeptidases, Humains, Maturation post-traductionnelle des protéines, Modèles moléculaires, Protéines de fusion recombinantes, Protéines virales, Sites de fixation, Structure moléculaire, Structure tertiaire des protéines.
English descriptors
- KwdEn :
- Binding Sites, Crystallography, X-Ray, Cysteine Endopeptidases, Endopeptidases (chemistry), Endopeptidases (genetics), Endopeptidases (metabolism), Humans, Models, Molecular, Molecular Structure, Protein Processing, Post-Translational, Protein Structure, Tertiary, Recombinant Fusion Proteins (chemistry), Recombinant Fusion Proteins (genetics), Recombinant Fusion Proteins (metabolism), SARS Virus (enzymology), Viral Proteins (antagonists & inhibitors), Viral Proteins (chemistry), Viral Proteins (genetics), Viral Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemistry : Endopeptidases, Recombinant Fusion Proteins, Viral Proteins.
- chemical , genetics : Endopeptidases, Recombinant Fusion Proteins, Viral Proteins.
- chemical , metabolism : Endopeptidases, Recombinant Fusion Proteins, Viral Proteins.
- chemical : Cysteine Endopeptidases.
- enzymology : SARS Virus.
- Binding Sites, Crystallography, X-Ray, Humans, Models, Molecular, Molecular Structure, Protein Processing, Post-Translational, Protein Structure, Tertiary.
Abstract
Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel human coronavirus. Viral maturation requires a main protease (3CL(pro)) to cleave the virus-encoded polyproteins. We report here that the 3CL(pro) containing additional N- and/or C-terminal segments of the polyprotein sequences undergoes autoprocessing and yields the mature protease in vitro. The dimeric three-dimensional structure of the C145A mutant protease shows that the active site of one protomer binds with the C-terminal six amino acids of the protomer from another asymmetric unit, mimicking the product-bound form and suggesting a possible mechanism for maturation. The P1 pocket of the active site binds the Gln side chain specifically, and the P2 and P4 sites are clustered together to accommodate large hydrophobic side chains. The tagged C145A mutant protein served as a substrate for the wild-type protease, and the N terminus was first digested (55-fold faster) at the Gln(-1)-Ser1 site followed by the C-terminal cleavage at the Gln306-Gly307 site. Analytical ultracentrifuge of the quaternary structures of the tagged and mature proteases reveals the remarkably tighter dimer formation for the mature enzyme (K(d) = 0.35 nm) than for the mutant (C145A) containing 10 extra N-terminal (K(d) = 17.2 nM) or C-terminal amino acids (K(d) = 5.6 nM). The data indicate that immature 3CL(pro) can form dimer enabling it to undergo autoprocessing to yield the mature enzyme, which further serves as a seed for facilitated maturation. Taken together, this study provides insights into the maturation process of the SARS 3CL(pro) from the polyprotein and design of new structure-based inhibitors.
DOI: 10.1074/jbc.M502577200
PubMed: 15788388
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002822
- to stream PubMed, to step Curation: 002822
- to stream PubMed, to step Checkpoint: 002632
- to stream Ncbi, to step Merge: 000E60
- to stream Ncbi, to step Curation: 000E60
- to stream Ncbi, to step Checkpoint: 000E60
Links to Exploration step
pubmed:15788388Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mechanism of the maturation process of SARS-CoV 3CL protease.</title><author><name sortKey="Hsu, Min Feng" sort="Hsu, Min Feng" uniqKey="Hsu M" first="Min-Feng" last="Hsu">Min-Feng Hsu</name><affiliation><nlm:affiliation>Institute of Biochemical Sciences, National Taiwan University, Taipei 106.</nlm:affiliation><wicri:noCountry code="subField">Taipei 106</wicri:noCountry></affiliation></author><author><name sortKey="Kuo, Chih Jung" sort="Kuo, Chih Jung" uniqKey="Kuo C" first="Chih-Jung" last="Kuo">Chih-Jung Kuo</name></author><author><name sortKey="Chang, Kai Ti" sort="Chang, Kai Ti" uniqKey="Chang K" first="Kai-Ti" last="Chang">Kai-Ti Chang</name></author><author><name sortKey="Chang, Hui Chuan" sort="Chang, Hui Chuan" uniqKey="Chang H" first="Hui-Chuan" last="Chang">Hui-Chuan Chang</name></author><author><name sortKey="Chou, Chia Cheng" sort="Chou, Chia Cheng" uniqKey="Chou C" first="Chia-Cheng" last="Chou">Chia-Cheng Chou</name></author><author><name sortKey="Ko, Tzu Ping" sort="Ko, Tzu Ping" uniqKey="Ko T" first="Tzu-Ping" last="Ko">Tzu-Ping Ko</name></author><author><name sortKey="Shr, Hui Lin" sort="Shr, Hui Lin" uniqKey="Shr H" first="Hui-Lin" last="Shr">Hui-Lin Shr</name></author><author><name sortKey="Chang, Gu Gang" sort="Chang, Gu Gang" uniqKey="Chang G" first="Gu-Gang" last="Chang">Gu-Gang Chang</name></author><author><name sortKey="Wang, Andrew H J" sort="Wang, Andrew H J" uniqKey="Wang A" first="Andrew H-J" last="Wang">Andrew H-J Wang</name></author><author><name sortKey="Liang, Po Huang" sort="Liang, Po Huang" uniqKey="Liang P" first="Po-Huang" last="Liang">Po-Huang Liang</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2005">2005</date><idno type="RBID">pubmed:15788388</idno><idno type="pmid">15788388</idno><idno type="doi">10.1074/jbc.M502577200</idno><idno type="wicri:Area/PubMed/Corpus">002822</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002822</idno><idno type="wicri:Area/PubMed/Curation">002822</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002822</idno><idno type="wicri:Area/PubMed/Checkpoint">002632</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002632</idno><idno type="wicri:Area/Ncbi/Merge">000E60</idno><idno type="wicri:Area/Ncbi/Curation">000E60</idno><idno type="wicri:Area/Ncbi/Checkpoint">000E60</idno><idno type="wicri:doubleKey">0021-9258:2005:Hsu M:mechanism:of:the</idno><idno type="wicri:Area/Main/Merge">004A43</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Mechanism of the maturation process of SARS-CoV 3CL protease.</title><author><name sortKey="Hsu, Min Feng" sort="Hsu, Min Feng" uniqKey="Hsu M" first="Min-Feng" last="Hsu">Min-Feng Hsu</name><affiliation><nlm:affiliation>Institute of Biochemical Sciences, National Taiwan University, Taipei 106.</nlm:affiliation><wicri:noCountry code="subField">Taipei 106</wicri:noCountry></affiliation></author><author><name sortKey="Kuo, Chih Jung" sort="Kuo, Chih Jung" uniqKey="Kuo C" first="Chih-Jung" last="Kuo">Chih-Jung Kuo</name></author><author><name sortKey="Chang, Kai Ti" sort="Chang, Kai Ti" uniqKey="Chang K" first="Kai-Ti" last="Chang">Kai-Ti Chang</name></author><author><name sortKey="Chang, Hui Chuan" sort="Chang, Hui Chuan" uniqKey="Chang H" first="Hui-Chuan" last="Chang">Hui-Chuan Chang</name></author><author><name sortKey="Chou, Chia Cheng" sort="Chou, Chia Cheng" uniqKey="Chou C" first="Chia-Cheng" last="Chou">Chia-Cheng Chou</name></author><author><name sortKey="Ko, Tzu Ping" sort="Ko, Tzu Ping" uniqKey="Ko T" first="Tzu-Ping" last="Ko">Tzu-Ping Ko</name></author><author><name sortKey="Shr, Hui Lin" sort="Shr, Hui Lin" uniqKey="Shr H" first="Hui-Lin" last="Shr">Hui-Lin Shr</name></author><author><name sortKey="Chang, Gu Gang" sort="Chang, Gu Gang" uniqKey="Chang G" first="Gu-Gang" last="Chang">Gu-Gang Chang</name></author><author><name sortKey="Wang, Andrew H J" sort="Wang, Andrew H J" uniqKey="Wang A" first="Andrew H-J" last="Wang">Andrew H-J Wang</name></author><author><name sortKey="Liang, Po Huang" sort="Liang, Po Huang" uniqKey="Liang P" first="Po-Huang" last="Liang">Po-Huang Liang</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="ISSN">0021-9258</idno><imprint><date when="2005" type="published">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Binding Sites</term><term>Crystallography, X-Ray</term><term>Cysteine Endopeptidases</term><term>Endopeptidases (chemistry)</term><term>Endopeptidases (genetics)</term><term>Endopeptidases (metabolism)</term><term>Humans</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Protein Processing, Post-Translational</term><term>Protein Structure, Tertiary</term><term>Recombinant Fusion Proteins (chemistry)</term><term>Recombinant Fusion Proteins (genetics)</term><term>Recombinant Fusion Proteins (metabolism)</term><term>SARS Virus (enzymology)</term><term>Viral Proteins (antagonists & inhibitors)</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cristallographie aux rayons X</term><term>Cysteine endopeptidases</term><term>Endopeptidases ()</term><term>Endopeptidases (génétique)</term><term>Endopeptidases (métabolisme)</term><term>Humains</term><term>Maturation post-traductionnelle des protéines</term><term>Modèles moléculaires</term><term>Protéines de fusion recombinantes ()</term><term>Protéines de fusion recombinantes (génétique)</term><term>Protéines de fusion recombinantes (métabolisme)</term><term>Protéines virales ()</term><term>Protéines virales (antagonistes et inhibiteurs)</term><term>Protéines virales (génétique)</term><term>Protéines virales (métabolisme)</term><term>Sites de fixation</term><term>Structure moléculaire</term><term>Structure tertiaire des protéines</term><term>Virus du SRAS (enzymologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Endopeptidases</term><term>Recombinant Fusion Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Endopeptidases</term><term>Recombinant Fusion Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Endopeptidases</term><term>Recombinant Fusion Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Cysteine Endopeptidases</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines virales</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="génétique" xml:lang="fr"><term>Endopeptidases</term><term>Protéines de fusion recombinantes</term><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Endopeptidases</term><term>Protéines de fusion recombinantes</term><term>Protéines virales</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>Crystallography, X-Ray</term><term>Humans</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Protein Processing, Post-Translational</term><term>Protein Structure, Tertiary</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cristallographie aux rayons X</term><term>Cysteine endopeptidases</term><term>Endopeptidases</term><term>Humains</term><term>Maturation post-traductionnelle des protéines</term><term>Modèles moléculaires</term><term>Protéines de fusion recombinantes</term><term>Protéines virales</term><term>Sites de fixation</term><term>Structure moléculaire</term><term>Structure tertiaire des protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel human coronavirus. Viral maturation requires a main protease (3CL(pro)) to cleave the virus-encoded polyproteins. We report here that the 3CL(pro) containing additional N- and/or C-terminal segments of the polyprotein sequences undergoes autoprocessing and yields the mature protease in vitro. The dimeric three-dimensional structure of the C145A mutant protease shows that the active site of one protomer binds with the C-terminal six amino acids of the protomer from another asymmetric unit, mimicking the product-bound form and suggesting a possible mechanism for maturation. The P1 pocket of the active site binds the Gln side chain specifically, and the P2 and P4 sites are clustered together to accommodate large hydrophobic side chains. The tagged C145A mutant protein served as a substrate for the wild-type protease, and the N terminus was first digested (55-fold faster) at the Gln(-1)-Ser1 site followed by the C-terminal cleavage at the Gln306-Gly307 site. Analytical ultracentrifuge of the quaternary structures of the tagged and mature proteases reveals the remarkably tighter dimer formation for the mature enzyme (K(d) = 0.35 nm) than for the mutant (C145A) containing 10 extra N-terminal (K(d) = 17.2 nM) or C-terminal amino acids (K(d) = 5.6 nM). The data indicate that immature 3CL(pro) can form dimer enabling it to undergo autoprocessing to yield the mature enzyme, which further serves as a seed for facilitated maturation. Taken together, this study provides insights into the maturation process of the SARS 3CL(pro) from the polyprotein and design of new structure-based inhibitors.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 004A43 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Merge/biblio.hfd -nk 004A43 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Main
|étape= Merge
|type= RBID
|clé= pubmed:15788388
|texte= Mechanism of the maturation process of SARS-CoV 3CL protease.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Merge/RBID.i -Sk "pubmed:15788388" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Merge/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |