› 3v3m

X-ray diffraction
1.96Å resolution

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease in Complex with N-[(1R)-2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl]-N-(4-tert-butylphenyl)furan-2-carboxamide inhibitor.

Released:
DOI: 10.2210/pdb3v3m/pdb
PDB entry 3v3m coloured by chain, front view.
PDB entry 3v3m coloured by chain, side view.
PDB entry 3v3m coloured by chain, top view.
Source organism: Severe acute respiratory syndrome-related coronavirus
Primary publication:
Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease.
Jacobs J, Grum-Tokars V, Zhou Y, Turlington M, Saldanha SA, Chase P, Eggler A, Dawson ES, Baez-Santos YM, Tomar S, Mielech AM, Baker SC, Lindsley CW, Hodder P, Mesecar A, Stauffer SR
J Med Chem 56 534-46 (2013)
PMID: 23231439

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

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-143077 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
3C-like proteinase nsp5 Chain: A
Molecule details ›
Chain: A
Length: 306 amino acids
Theoretical weight: 33.88 KDa
Source organism: Severe acute respiratory syndrome-related coronavirus
Expression system: Homo sapiens
UniProt:
  • Canonical: P0C6U8 (Residues: 3241-3546; Coverage: 7%)
Gene name: 1a
Sequence domains: Coronavirus endopeptidase C30
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand 0EN 1 x 0EN
Ligand DMS 2 x DMS
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-G
Spacegroup: C2
Unit cell:
a: 106.733Å b: 82.668Å c: 53.117Å
α: 90° β: 106.03° γ: 90°
R-values:
R R work R free
0.191 0.189 0.236
Expression system: Homo sapiens

Quick links

Citations

30 review citations

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

45 mentions without citation

An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy.
Pillaiyar et al. (2016)
44 more