› 2ydk

X-ray diffraction
1.9Å resolution

Discovery of Checkpoint Kinase Inhibitor AZD7762 by Structure Based Design and Optimization of Thiophene Carboxamide Ureas

Released:
DOI: 10.2210/pdb2ydk/pdb
PDB entry 2ydk coloured by chain, front view.
PDB entry 2ydk coloured by chain, side view.
PDB entry 2ydk coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of checkpoint kinase inhibitor (S)-5-(3-fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide (AZD7762) by structure-based design and optimization of thiophenecarboxamide ureas.
Oza V, Ashwell S, Almeida L, Brassil P, Breed J, Deng C, Gero T, Grondine M, Horn C, Ioannidis S, Liu D, Lyne P, Newcombe N, Pass M, Read J, Ready S, Rowsell S, Su M, Toader D, Vasbinder M, Yu D, Yu Y, Xue Y, Zabludoff S, Janetka J
J Med Chem 55 5130-42 (2012)
PMID: 22551018

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-127093 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Serine/threonine-protein kinase Chk1 Chain: A
Molecule details ›
Chain: A
Length: 276 amino acids
Theoretical weight: 31.84 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O14757 (Residues: 1-276; Coverage: 58%)
Gene names: CHEK1, CHK1
Sequence domains: Protein kinase domain
Structure domains:

Ligands and Environments

3 bound ligands:
Ligand SO4 1 x SO4
Ligand GOL 5 x GOL
Ligand YDK 1 x YDK
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID14-4
Spacegroup: P212121
Unit cell:
a: 41.613Å b: 70.791Å c: 104.063Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.183 0.181 0.226
Expression system: Spodoptera frugiperda

Quick links

Citations

10 review citations

CHEK again: revisiting the development of CHK1 inhibitors for cancer therapy.
McNeely et al. (2014)
9 more

1 mention without citation

Moving Beyond Active-Site Detection: MixMD Applied to Allosteric Systems.
Ghanakota et al. (2016)