2FE8

SARS coronavirus papain-like protease: structure of a viral deubiquitinating enzyme

Summary for 2FE8

• Entry DOI: 10.2210/pdb2fe8/pdb
• Descriptor: Replicase polyprotein 1ab, ZINC ION, BROMIDE ION, ... (5 entities in total)
• Functional Keywords: protease, hydrolase
• Biological source: SARS coronavirus
• Total number of polymer chains: 3
• Total formula weight: 107376.83

Authors

Ratia, K.,Santarsiero, B.D.,Mesecar, A.D. (deposition date: 2005-12-15, release date: 2006-03-21, Last modification date: 2024-02-14)

Primary citation

Ratia, K.,Saikatendu, K.S.,Santarsiero, B.D.,Barretto, N.,Baker, S.C.,Stevens, R.C.,Mesecar, A.D.
Severe acute respiratory syndrome coronavirus papain-like protease: Structure of a viral deubiquitinating enzyme
Proc.Natl.Acad.Sci.Usa, 103:5717-5722, 2006

PubMed 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.

PubMed: 16581910
DOI: 10.1073/pnas.0510851103

Experimental method

X-RAY DIFFRACTION (1.85 Å)