Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme.
Identifieur interne : 003D08 ( Main/Exploration ); précédent : 003D07; suivant : 003D09Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme.
Auteurs : Kiira Ratia [États-Unis] ; Kumar Singh Saikatendu ; Bernard D. Santarsiero ; Naina Barretto ; Susan C. Baker ; Raymond C. Stevens ; Andrew D. MesecarSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2006.
Descripteurs français
- KwdFr :
- MESH :
- enzymologie : Virus du SRAS.
- métabolisme : Papaïne, Peptide hydrolases, Ubiquitine.
- Cristallographie aux rayons X, Cysteine endopeptidases, Modèles moléculaires, Protéines virales, Sites de fixation, Structure secondaire des protéines.
English descriptors
- KwdEn :
- MESH :
- chemical , chemistry : Cysteine Endopeptidases, Viral Proteins.
- chemical , metabolism : Papain, Peptide Hydrolases, Ubiquitin.
- enzymology : SARS Virus.
- Binding Sites, Crystallography, X-Ray, Models, Molecular, Protein Structure, Secondary.
Abstract
Replication of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) requires proteolytic processing of the replicase polyprotein by two viral cysteine proteases, a chymotrypsin-like protease (3CLpro) and a papain-like protease (PLpro). These proteases are important targets for development of antiviral drugs that would inhibit viral replication and reduce mortality associated with outbreaks of SARS-CoV. In this work, we describe the 1.85-A crystal structure of the catalytic core of SARS-CoV PLpro and show that the overall architecture adopts a fold closely resembling that of known deubiquitinating enzymes. Key features, however, distinguish PLpro from characterized deubiquitinating enzymes, including an intact zinc-binding motif, an unobstructed catalytically competent active site, and the presence of an intriguing, ubiquitin-like N-terminal domain. To gain insight into the active-site recognition of the C-terminal tail of ubiquitin and the related LXGG motif, we propose a model of PLpro in complex with ubiquitin-aldehyde that reveals well defined sites within the catalytic cleft that help to account for strict substrate-recognition motifs.
DOI: 10.1073/pnas.0510851103
PubMed: 16581910
Affiliations:
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Santarsiero</name></author><author><name sortKey="Barretto, Naina" sort="Barretto, Naina" uniqKey="Barretto N" first="Naina" last="Barretto">Naina Barretto</name></author><author><name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C" last="Baker">Susan C. Baker</name></author><author><name sortKey="Stevens, Raymond C" sort="Stevens, Raymond C" uniqKey="Stevens R" first="Raymond C" last="Stevens">Raymond C. Stevens</name></author><author><name sortKey="Mesecar, Andrew D" sort="Mesecar, Andrew D" uniqKey="Mesecar A" first="Andrew D" last="Mesecar">Andrew D. Mesecar</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</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>Crystallography, X-Ray</term><term>Cysteine Endopeptidases (chemistry)</term><term>Models, Molecular</term><term>Papain (metabolism)</term><term>Peptide Hydrolases (metabolism)</term><term>Protein Structure, Secondary</term><term>SARS Virus (enzymology)</term><term>Ubiquitin (metabolism)</term><term>Viral Proteins (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cristallographie aux rayons X</term><term>Cysteine endopeptidases ()</term><term>Modèles moléculaires</term><term>Papaïne (métabolisme)</term><term>Peptide hydrolases (métabolisme)</term><term>Protéines virales ()</term><term>Sites de fixation</term><term>Structure secondaire des protéines</term><term>Ubiquitine (métabolisme)</term><term>Virus du SRAS (enzymologie)</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>Papain</term><term>Peptide Hydrolases</term><term>Ubiquitin</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="métabolisme" xml:lang="fr"><term>Papaïne</term><term>Peptide hydrolases</term><term>Ubiquitine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>Crystallography, X-Ray</term><term>Models, Molecular</term><term>Protein Structure, Secondary</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cristallographie aux rayons X</term><term>Cysteine endopeptidases</term><term>Modèles moléculaires</term><term>Protéines virales</term><term>Sites de fixation</term><term>Structure secondaire des protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Replication of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) requires proteolytic processing of the replicase polyprotein by two viral cysteine proteases, a chymotrypsin-like protease (3CLpro) and a papain-like protease (PLpro). These proteases are important targets for development of antiviral drugs that would inhibit viral replication and reduce mortality associated with outbreaks of SARS-CoV. In this work, we describe the 1.85-A crystal structure of the catalytic core of SARS-CoV PLpro and show that the overall architecture adopts a fold closely resembling that of known deubiquitinating enzymes. Key features, however, distinguish PLpro from characterized deubiquitinating enzymes, including an intact zinc-binding motif, an unobstructed catalytically competent active site, and the presence of an intriguing, ubiquitin-like N-terminal domain. To gain insight into the active-site recognition of the C-terminal tail of ubiquitin and the related LXGG motif, we propose a model of PLpro in complex with ubiquitin-aldehyde that reveals well defined sites within the catalytic cleft that help to account for strict substrate-recognition motifs.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li></region></list><tree><noCountry><name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C" last="Baker">Susan C. Baker</name><name sortKey="Barretto, Naina" sort="Barretto, Naina" uniqKey="Barretto N" first="Naina" last="Barretto">Naina Barretto</name><name sortKey="Mesecar, Andrew D" sort="Mesecar, Andrew D" uniqKey="Mesecar A" first="Andrew D" last="Mesecar">Andrew D. Mesecar</name><name sortKey="Saikatendu, Kumar Singh" sort="Saikatendu, Kumar Singh" uniqKey="Saikatendu K" first="Kumar Singh" last="Saikatendu">Kumar Singh Saikatendu</name><name sortKey="Santarsiero, Bernard D" sort="Santarsiero, Bernard D" uniqKey="Santarsiero B" first="Bernard D" last="Santarsiero">Bernard D. Santarsiero</name><name sortKey="Stevens, Raymond C" sort="Stevens, Raymond C" uniqKey="Stevens R" first="Raymond C" last="Stevens">Raymond C. Stevens</name></noCountry><country name="États-Unis"><region name="Illinois"><name sortKey="Ratia, Kiira" sort="Ratia, Kiira" uniqKey="Ratia K" first="Kiira" last="Ratia">Kiira Ratia</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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