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X-ray diffraction
2.63Å resolution

Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease Inhibitors: Design, Synthesis, Protein-Ligand X-ray Structure and Biological Evaluation

Released:
DOI: 10.2210/pdb3mj5/pdb
PDB entry 3mj5 coloured by chain, front view.
PDB entry 3mj5 coloured by chain, side view.
PDB entry 3mj5 coloured by chain, top view.
Source organism: Severe acute respiratory syndrome-related coronavirus
Primary publication:
Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biological evaluation.
Ghosh AK, Takayama J, Rao KV, Ratia K, Chaudhuri R, Mulhearn DC, Lee H, Nichols DB, Baliji S, Baker SC, Johnson ME, Mesecar AD
J Med Chem 53 4968-79 (2010)
PMID: 20527968

Function and Biology Details

Reactions catalysed: 
GTP + a 5'-diphospho-[mRNA] = diphosphate + a 5'-(5'-triphosphoguanosine)-[mRNA]
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assemblies composition:
monomeric (preferred)
homo dimer
Assembly name:
PDBe Complex ID:
PDB-CPX-143071 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Papain-like protease nsp3 Chains: A, B
Molecule details ›
Chains: A, B
Length: 316 amino acids
Theoretical weight: 35.52 KDa
Source organism: Severe acute respiratory syndrome-related coronavirus
Expression system: Escherichia coli
UniProt:
  • Canonical: P0C6U8 (Residues: 1541-1855; Coverage: 7%)
Gene name: 1a
Sequence domains: Coronavirus papain-like peptidase
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand GRM 2 x GRM
Ligand ZN 2 x ZN
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 22-BM
Spacegroup: C2
Unit cell:
a: 118.397Å b: 74.129Å c: 96.895Å
α: 90° β: 103.02° γ: 90°
R-values:
R R work R free
0.211 0.208 0.248
Expression system: Escherichia coli

Quick links

Citations

31 review citations

From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design.
Hilgenfeld R. (2014)
30 more

37 mentions without citation

The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds.
Báez-Santos et al. (2015)
36 more