› 4x7o

X-ray diffraction
2.65Å resolution

Co-crystal Structure of PERK bound to 1-[5-(4-amino-2,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-indol-1-yl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]ethanone inhibitor

Released:
DOI: 10.2210/pdb4x7o/pdb
PDB 4x7o coloured by chain and viewed from the front.
PDB 4x7o coloured by chain and viewed from the side.
PDB 4x7o coloured by chain and viewed from the top.
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. (2015)
PMID: 25587754

Function and Biology Details

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

Structure analysis Details

Assembly composition:
monomeric (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

1 bound ligand:
Ligand 3Z6 1 x 3Z6
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P3221
Unit cell:
a: 125.366Å b: 125.366Å c: 58.203Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.2 0.199 0.226
Expression system: Escherichia coli

Quick links

Citations

12 review citations

Chemical Chaperones to Inhibit Endoplasmic Reticulum Stress: Implications in Diseases.
Jeon et al. (2022)
11 more

1 mention without citation

Optimization of a Novel Mandelamide-Derived Pyrrolopyrimidine Series of PERK Inhibitors.
Stokes et al. (2022)