› 5hbe

X-ray diffraction
2.38Å resolution

CDK8-CYCC IN COMPLEX WITH 8-[3-Chloro-5-(1-methyl-2,2-dioxo-2, 3-dihydro-1H-2l6-benzo[c]isothiazol-5-yl)-pyridin- 4-yl]-1-oxa-3,8-diaza-spiro[4.5]decan-2-one

Released:
DOI: 10.2210/pdb5hbe/pdb
PDB entry 5hbe coloured by chain, front view.
PDB entry 5hbe coloured by chain, side view.
PDB entry 5hbe coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19.
Mallinger A, Schiemann K, Rink C, Stieber F, Calderini M, Crumpler S, Stubbs M, Adeniji-Popoola O, Poeschke O, Busch M, Czodrowski P, Musil D, Schwarz D, Ortiz-Ruiz MJ, Schneider R, Thai C, Valenti M, de Haven Brandon A, Burke R, Workman P, Dale T, Wienke D, Clarke PA, Esdar C, Raynaud FI, Eccles SA, Rohdich F, Blagg J
J Med Chem 59 1078-101 (2016)
PMID: 26796641

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: 266 amino acids
Theoretical weight: 31.54 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

4 bound ligands:
Ligand 5Y6 1 x 5Y6
Ligand DMS 1 x DMS
Ligand EDO 1 x EDO
Ligand FMT 4 x FMT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06SA
Spacegroup: P212121
Unit cell:
a: 71.007Å b: 71.115Å c: 173.152Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.23 0.229 0.256
Expression system: Spodoptera frugiperda

Quick links

Citations

9 review citations

Inhibitors of cyclin-dependent kinases as cancer therapeutics.
Whittaker et al. (2017)
8 more

3 mentions without citation

Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19.
Mallinger et al. (2016)
2 more