Download MendeleyStructural basis for catalysis and ubiquitin recognition by the severe acute respiratory syndrome coronavirus papain-like protease
Chou, C.-Y., Lai, H.-Y., Chen, H.-Y., Cheng, S.-C., Cheng, K.-W., Chou, Y.-W.(2014) Acta Crystallogr D Biol Crystallogr 70: 572-581
- PubMed: 24531491
- DOI: https://doi.org/10.1107/S1399004713031040
- Primary Citation of Related Structures:
4M0W - 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?? 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.
Organizational Affiliation:
Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Tapei 112, Taiwan.
