2fe8
From Proteopedia
(New page: 200px<br /><applet load="2fe8" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fe8, resolution 1.85Å" /> '''SARS coronavirus pap...) |
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- | [[Image:2fe8.gif|left|200px]]<br /><applet load="2fe8" size=" | + | [[Image:2fe8.gif|left|200px]]<br /><applet load="2fe8" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2fe8, resolution 1.85Å" /> | caption="2fe8, resolution 1.85Å" /> | ||
'''SARS coronavirus papain-like protease: structure of a viral deubiquitinating enzyme'''<br /> | '''SARS coronavirus papain-like protease: structure of a viral deubiquitinating enzyme'''<br /> | ||
==Overview== | ==Overview== | ||
- | Replication of severe acute respiratory syndrome (SARS) coronavirus | + | 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. |
==About this Structure== | ==About this Structure== | ||
- | 2FE8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus] with ZN, BR and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2FE8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=BR:'>BR</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FE8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Sars coronavirus]] | [[Category: Sars coronavirus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
- | [[Category: Mesecar, A | + | [[Category: Mesecar, A D.]] |
[[Category: Ratia, K.]] | [[Category: Ratia, K.]] | ||
- | [[Category: Santarsiero, B | + | [[Category: Santarsiero, B D.]] |
[[Category: BR]] | [[Category: BR]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: protease]] | [[Category: protease]] | ||
- | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:20:35 2008'' |
Revision as of 15:20, 21 February 2008
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SARS coronavirus papain-like protease: structure of a viral deubiquitinating enzyme
Overview
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.
About this Structure
2FE8 is a Single protein structure of sequence from Sars coronavirus with , and as ligands. Full crystallographic information is available from OCA.
Reference
Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme., Ratia K, Saikatendu KS, Santarsiero BD, Barretto N, Baker SC, Stevens RC, Mesecar AD, Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5717-22. Epub 2006 Mar 31. PMID:16581910
Page seeded by OCA on Thu Feb 21 17:20:35 2008
Categories: Sars coronavirus | Single protein | Mesecar, A D. | Ratia, K. | Santarsiero, B D. | BR | SO4 | ZN | Protease