› 5bnj

X-ray diffraction
2.64Å resolution

CDK8/CYCC IN COMPLEX WITH 8-{3-Chloro-5-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyridin- 4-yl}-2,8-diaza-spiro[4.5]decan-1-one

Released:
DOI: 10.2210/pdb5bnj/pdb
PDB entry 5bnj coloured by chain, front view.
PDB entry 5bnj coloured by chain, side view.
PDB entry 5bnj coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease.
Dale T, Clarke PA, Esdar C, Waalboer D, Adeniji-Popoola O, Ortiz-Ruiz MJ, Mallinger A, Samant RS, Czodrowski P, Musil D, Schwarz D, Schneider K, Stubbs M, Ewan K, Fraser E, TePoele R, Court W, Box G, Valenti M, de Haven Brandon A, Gowan S, Rohdich F, Raynaud F, Schneider R, Poeschke O, Blaukat A, Workman P, Schiemann K, Eccles SA, Wienke D, Blagg J
Nat Chem Biol 11 973-980 (2015)
PMID: 26502155

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: 405 amino acids
Theoretical weight: 46.99 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P49336 (Residues: 1-403; Coverage: 87%)
Gene name: CDK8
Sequence domains: Protein kinase domain
Structure domains:
Cyclin-C Chain: B
Molecule details ›
Chain: B
Length: 285 amino acids
Theoretical weight: 33.48 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P24863 (Residues: 1-283; Coverage: 100%)
Gene name: CCNC
Sequence domains:
Structure domains: Cyclin-like

Ligands and Environments

2 bound ligands:
Ligand 4TV 1 x 4TV
Ligand FMT 2 x FMT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06DA
Spacegroup: P212121
Unit cell:
a: 70.787Å b: 71.489Å c: 172.532Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.228 0.226 0.273
Expression system: Spodoptera frugiperda

Quick links

Citations

22 review citations

Kinase inhibitors: the road ahead.
Ferguson et al. (2018)
21 more

6 mentions without citation

Structure-based drug design: aiming for a perfect fit.
van Montfort et al. (2017)
5 more