› 5icp

X-ray diffraction
2.18Å resolution

CDK8-CYCC IN COMPLEX WITH [(S)-2-(4-Chloro-phenyl)-pyrrolidin-1-yl]-(5-methyl-imidazo[5,1-b][1,3,4]thiadiazol-2-yl)-methanone

Released:
DOI: 10.2210/pdb5icp/pdb
PDB entry 5icp coloured by chain, front view.
PDB entry 5icp coloured by chain, side view.
PDB entry 5icp coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening.
Czodrowski P, Mallinger A, Wienke D, Esdar C, Pöschke O, Busch M, Rohdich F, Eccles SA, Ortiz-Ruiz MJ, Schneider R, Raynaud FI, Clarke PA, Musil D, Schwarz D, Dale T, Urbahns K, Blagg J, Schiemann K
J Med Chem 59 9337-9349 (2016)
PMID: 27490956

Function and Biology Details

Reactions catalysed: 
ATP + a protein = ADP + a phosphoprotein
ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-150300 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Cyclin-dependent kinase 8 Chain: A
Molecule details ›
Chain: A
Length: 364 amino acids
Theoretical weight: 42.55 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P49336 (Residues: 1-362; Coverage: 78%)
Gene name: CDK8
Sequence domains: Protein kinase domain
Structure domains:
Cyclin-C Chain: B
Molecule details ›
Chain: B
Length: 267 amino acids
Theoretical weight: 31.66 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P24863 (Residues: 1-264; Coverage: 93%)
Gene name: CCNC
Sequence domains:
Structure domains: Cyclin-like

Ligands and Environments

3 bound ligands:
Ligand 69Z 1 x 69Z
Ligand EDO 3 x EDO
Ligand FMT 9 x FMT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06SA
Spacegroup: P212121
Unit cell:
a: 70.39Å b: 70.391Å c: 168.739Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.185 0.184 0.216
Expression system: Spodoptera frugiperda

Quick links

Citations

13 review citations

Kinase inhibition in autoimmunity and inflammation.
Zarrin et al. (2021)
12 more

1 mention without citation

Structure-based discovery of cyclin-dependent protein kinase inhibitors.
Martin et al. (2017)