› 4cfu

X-ray diffraction
2.2Å resolution

Structure-based design of C8-substituted O6-cyclohexylmethoxyguanine CDK1 and 2 inhibitors.

Released:
DOI: 10.2210/pdb4cfu/pdb
PDB entry 4cfu coloured by chain, front view.
PDB entry 4cfu coloured by chain, side view.
PDB entry 4cfu coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
8-Substituted O(6)-cyclohexylmethylguanine CDK2 inhibitors: using structure-based inhibitor design to optimize an alternative binding mode.
Carbain B, Paterson DJ, Anscombe E, Campbell AJ, Cano C, Echalier A, Endicott JA, Golding BT, Haggerty K, Hardcastle IR, Jewsbury PJ, Newell DR, Noble ME, Roche C, Wang LZ, Griffin RJ
J Med Chem 57 56-70 (2014)
PMID: 24304238

Function and Biology Details

Reaction catalysed: 
ATP + a protein = ADP + a phosphoprotein
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-148886 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
Cyclin-dependent kinase 2 Chains: A, C
Molecule details ›
Chains: A, C
Length: 303 amino acids
Theoretical weight: 34.45 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli B
UniProt:
  • Canonical: P24941 (Residues: 1-298; Coverage: 100%)
Gene names: CDK2, CDKN2
Sequence domains: Protein kinase domain
Structure domains:
Cyclin-A2 Chain: B
Molecule details ›
Chain: B
Length: 262 amino acids
Theoretical weight: 30 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli B
UniProt:
  • Canonical: P20248 (Residues: 172-432; Coverage: 60%)
Gene names: CCN1, CCNA, CCNA2
Sequence domains:
Structure domains: Cyclin-like
Cyclin-A2 Chain: D
Molecule details ›
Chain: D
Length: 262 amino acids
Theoretical weight: 30.09 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli B
UniProt:
  • Canonical: P20248 (Residues: 173-432; Coverage: 60%)
Gene names: CCN1, CCNA, CCNA2
Sequence domains:
Structure domains: Cyclin-like

Ligands and Environments

2 bound ligands:
Ligand 2WC 2 x 2WC
Ligand MG 2 x MG
1 modified residue:
Ligand TPO 2 x TPO

Experiments and Validation Details

Entry percentile scores
X-ray source: ELETTRA BEAMLINE 5.2R
Spacegroup: P212121
Unit cell:
a: 73.806Å b: 133.744Å c: 147.46Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.184 0.182 0.221
Expression system: Escherichia coli B

Quick links

Citations

6 citation in other articles

Inhibitory Kappa B Kinase α (IKKα) Inhibitors That Recapitulate Their Selectivity in Cells against Isoform-Related Biomarkers.
Anthony et al. (2017)
5 more

2 mentions without citation

Effect of solvent and protein dynamics in ligand recognition and inhibition of aminoglycoside adenyltransferase 2″-Ia.
Bacot-Davis et al. (2017)
1 more