2fe8

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(New page: 200px<br /><applet load="2fe8" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fe8, resolution 1.85&Aring;" /> '''SARS coronavirus pap...)
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[[Image:2fe8.gif|left|200px]]<br /><applet load="2fe8" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:2fe8.gif|left|200px]]<br /><applet load="2fe8" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2fe8, resolution 1.85&Aring;" />
caption="2fe8, resolution 1.85&Aring;" />
'''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==
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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.
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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==
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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FE8 OCA].
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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]]
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[[Category: Mesecar, A.D.]]
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[[Category: Mesecar, A D.]]
[[Category: Ratia, K.]]
[[Category: Ratia, K.]]
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[[Category: Santarsiero, B.D.]]
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[[Category: Santarsiero, B D.]]
[[Category: BR]]
[[Category: BR]]
[[Category: SO4]]
[[Category: SO4]]
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[[Category: protease]]
[[Category: protease]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:30:34 2007''
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''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


2fe8, resolution 1.85Å

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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

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