4M0W: Crystal Structure Of Sars-cov Papain-like Protease C112s Mutant In Complex With Ubiquitin

Citation:
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 A 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.
PDB ID: 4M0WDownload
MMDB ID: 117491
PDB Deposition Date: 2013/8/2
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 1.4  Å
Source Organism:
SARS coronavirus
Similar Structures:
Biological Unit for 4M0W: dimeric; determined by author and by software (PISA)
Molecular Components in 4M0W
Label Count Molecule
Proteins (2 molecules)
1
Replicase Polyprotein 1A(Gene symbol: orf1ab)
Molecule annotation
1
Ubiquitin(Gene symbol: RPS27A)
Molecule annotation
Chemicals (7 molecules)
1
1
2
1
3
2
4
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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