› 6b3e

X-ray diffraction
3.06Å resolution

Crystal structure of human CDK12/CyclinK in complex with an inhibitor

Released:
DOI: 10.2210/pdb6b3e/pdb
PDB entry 6b3e coloured by chain, front view.
PDB entry 6b3e coloured by chain, side view.
PDB entry 6b3e coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-Based Design of Selective Noncovalent CDK12 Inhibitors.
Johannes JW, Denz CR, Su N, Wu A, Impastato AC, Mlynarski S, Varnes JG, Prince DB, Cidado J, Gao N, Haddrick M, Jones NH, Li S, Li X, Liu Y, Nguyen TB, O'Connell N, Rivers E, Robbins DW, Tomlinson R, Yao T, Zhu X, Ferguson AD, Lamb ML, Manchester JI, Guichard S
ChemMedChem 13 231-235 (2018)
PMID: 29266803

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:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-131171 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Cyclin-dependent kinase 12 Chains: A, C
Molecule details ›
Chains: A, C
Length: 320 amino acids
Theoretical weight: 37.13 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q9NYV4 (Residues: 717-1036; Coverage: 22%)
Gene names: CDK12, CRK7, CRKRS, KIAA0904
Sequence domains: Protein kinase domain
Structure domains:
Cyclin-K Chains: B, D
Molecule details ›
Chains: B, D
Length: 267 amino acids
Theoretical weight: 31.37 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O75909 (Residues: 1-267; Coverage: 46%)
Gene names: CCNK, CPR4
Sequence domains:
Structure domains: Cyclin-like

Ligands and Environments

3 bound ligands:
Ligand MG 2 x MG
Ligand CJM 2 x CJM
Ligand EDO 3 x EDO
1 modified residue:
Ligand TPO 2 x TPO

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P1
Unit cell:
a: 50.14Å b: 77.26Å c: 90.64Å
α: 76.53° β: 85.28° γ: 78.22°
R-values:
R R work R free
0.191 0.19 0.212
Expression system: Spodoptera frugiperda

Quick links

Citations

5 review citations

Therapeutic targeting of transcriptional cyclin-dependent kinases.
Galbraith et al. (2019)
4 more

1 mention without citation

Discovery and resistance mechanism of a selective CDK12 degrader.
Jiang et al. (2021)