› 4mds

X-ray diffraction
1.6Å resolution

Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and non-covalent nanomolar inhibitors with an induced-fit binding

Released:
DOI: 10.2210/pdb4mds/pdb
PDB entry 4mds coloured by chain, front view.
PDB entry 4mds coloured by chain, side view.
PDB entry 4mds coloured by chain, top view.
Source organism: Severe acute respiratory syndrome-related coronavirus
Primary publication:
Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding.
Turlington M, Chun A, Tomar S, Eggler A, Grum-Tokars V, Jacobs J, Daniels JS, Dawson E, Saldanha A, Chase P, Baez-Santos YM, Lindsley CW, Hodder P, Mesecar AD, Stauffer SR
OpenAccess logo Bioorg Med Chem Lett 23 6172-7 (2013)
PMID: 24080461

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: 303 amino acids
Theoretical weight: 33.47 KDa
Source organism: Severe acute respiratory syndrome-related coronavirus
Expression system: Escherichia coli
UniProt:
  • Canonical: P0C6U8 (Residues: 3241-3542; Coverage: 7%)
Gene name: 1a
Sequence domains: Coronavirus endopeptidase C30
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand 23H 1 x 23H
Ligand DMS 2 x DMS
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 22-ID
Spacegroup: C2
Unit cell:
a: 118.824Å b: 56.244Å c: 53.14Å
α: 90° β: 111.13° γ: 90°
R-values:
R R work R free
0.172 0.17 0.212
Expression system: Escherichia coli

Quick links

Citations

24 review citations

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

37 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)
36 more