Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme.

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.

authors

Ratia K,Saikatendu KS,Santarsiero BD,Barretto N,Baker SC,Stevens RC,Mesecar AD

doi

10.1073/pnas.0510851103

keywords:

subject

Has Abstract

pub_date

2006-04-11 00:00:00

pages

5717-22

issue

15

eissn

0027-8424

issn

1091-6490

pii

0510851103

journal_volume

103

pub_type

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