› 4x7k

X-ray diffraction
1.8Å resolution

Co-crystal Structure of PERK bound to 4-{2-amino-3-[5-fluoro-2-(methylamino)quinazolin-6-yl]-4-methylbenzoyl}-1-methyl-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one inhibitor

Released:
DOI: 10.2210/pdb4x7k/pdb
PDB entry 4x7k coloured by chain, front view.
PDB entry 4x7k coloured by chain, side view.
PDB entry 4x7k coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK).
Smith AL, Andrews KL, Beckmann H, Bellon SF, Beltran PJ, Booker S, Chen H, Chung YA, D'Angelo ND, Dao J, Dellamaggiore KR, Jaeckel P, Kendall R, Labitzke K, Long AM, Materna-Reichelt S, Mitchell P, Norman MH, Powers D, Rose M, Shaffer PL, Wu MM, Lipford JR
J Med Chem 58 1426-41 (2015)
PMID: 25587754

Function and Biology Details

Reaction catalysed: 
ATP + a protein = ADP + a phosphoprotein
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-192755 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Eukaryotic translation initiation factor 2-alpha kinase 3 Chain: A
Molecule details ›
Chain: A
Length: 317 amino acids
Theoretical weight: 36.82 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9NZJ5 (Residues: 575-1094; Coverage: 29%)
Gene names: EIF2AK3, PEK, PERK
Sequence domains: Protein kinase domain

Ligands and Environments

3 bound ligands:
Ligand 3Z3 1 x 3Z3
Ligand TLA 1 x TLA
Ligand GOL 1 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.1
Spacegroup: P41212
Unit cell:
a: 81.757Å b: 81.757Å c: 128.621Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.177 0.176 0.196
Expression system: Escherichia coli

Quick links

Citations

17 review citations

Endoplasmic reticulum stress signals in the tumour and its microenvironment.
Chen et al. (2021)
16 more

1 mention without citation

Triazolo[4,5-d]pyrimidines as Validated General Control Nonderepressible 2 (GCN2) Protein Kinase Inhibitors Reduce Growth of Leukemia Cells.
Lough et al. (2018)