4M0W

Crystal Structure of SARS-CoV papain-like protease C112S mutant in complex with ubiquitin

Summary for 4M0W

• Entry DOI: 10.2210/pdb4m0w/pdb
• Descriptor: Replicase polyprotein 1a, Ubiquitin, ZINC ION, ... (7 entities in total)
• Functional Keywords: papain-like protease-ubiquitin complex, protein hydrolase and deubiquitination, hydrolase-protein binding complex, hydrolase/protein binding
• Biological source: SARS coronavirus (SARS-CoV); More
• Cellular location: Non-structural protein 3: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 4: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 6: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 7: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 8: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 9: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 10: Host cytoplasm, host perinuclear region (By similarity): P0C6U8; Ubiquitin: Cytoplasm (By similarity): P62992
• Total number of polymer chains: 2
• Total formula weight: 46214.76

Authors

Chou, C.-Y.,Chen, H.-Y.,Lai, H.-Y.,Cheng, S.-C.,Chou, Y.-W. (deposition date: 2013-08-02, release date: 2014-02-12, Last modification date: 2023-11-08)

Primary citation

Chou, C.-Y.,Lai, H.-Y.,Chen, H.-Y.,Cheng, S.-C.,Cheng, K.-W.,Chou, Y.-W.
Structural basis for catalysis and ubiquitin recognition by the severe acute respiratory syndrome coronavirus papain-like protease
Acta Crystallogr.,Sect.D, 70:572-581, 2014

PubMed Abstract: Papain-like protease (PLpro) is one of two cysteine proteases involved in the proteolytic processing of the polyproteins of Severe acute respiratory syndrome coronavirus (SARS-CoV). PLpro also shows significant in vitro deubiquitinating and de-ISGylating activities, although the detailed mechanism is still unclear. Here, the crystal structure of SARS-CoV PLpro C112S mutant in complex with ubiquitin (Ub) is reported at 1.4 Å resolution. The Ub core makes mostly hydrophilic interactions with PLpro, while the Leu-Arg-Gly-Gly C-terminus of Ub is located in the catalytic cleft of PLpro, mimicking the P4-P1 residues and providing the first atomic insights into its catalysis. One of the O atoms of the C-terminal Gly residue of Ub is located in the oxyanion hole consisting of the main-chain amides of residues 112 and 113. Mutations of residues in the PLpro-Ub interface lead to reduced catalytic activity, confirming their importance for Ub binding and/or catalysis. The structure also revealed an N-cyclohexyl-2-aminethanesulfonic acid molecule near the catalytic triad, and kinetic studies suggest that this binding site is also used by other PLpro inhibitors. Overall, the structure provides a foundation for understanding the molecular basis of coronaviral PLpro catalysis.

PubMed: 24531491
DOI: 10.1107/S1399004713031040

Experimental method

X-RAY DIFFRACTION (1.4 Å)