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.
journal_name
Proc Natl Acad Sci U S Aauthors
Ratia K,Saikatendu KS,Santarsiero BD,Barretto N,Baker SC,Stevens RC,Mesecar ADdoi
10.1073/pnas.0510851103keywords:
subject
Has Abstractpub_date
2006-04-11 00:00:00pages
5717-22issue
15eissn
0027-8424issn
1091-6490pii
0510851103journal_volume
103pub_type
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