4CG9: Human Choline Kinase A1 In Complex With Compound 12

Human choline kinase alpha (CKalpha) is a validated drug target for the treatment of cancer. In recent years, a large number of CK inhibitors have been synthesized, and one of them is currently being evaluated in Phase I clinical trials as a treatment for solid tumors. Here we have evaluated a new series of asymmetrical biscationic CK inhibitors by means of enzymatic, crystallographic, and antitumor studies. We demonstrate that one of these structures adopts a completely new binding mode not observed before inducing the aperture of an adjacent binding site. This compound shows antiproliferative and apoptotic effects on cancer cells through activation of caspase-3. Therefore, this study not only provides fruitful insights into the design of more efficient compounds that may target different regions in CKalpha1 but also explains how these compounds induce apoptosis in cancer cells.
PDB ID: 4CG9Download
MMDB ID: 116599
PDB Deposition Date: 2013/11/21
Updated in MMDB: 2014/03
Experimental Method:
x-ray diffraction
Resolution: 1.83  Å
Source Organism:
Similar Structures:
Biological Unit for 4CG9: monomeric; determined by software (PISA)
Molecular Components in 4CG9
Label Count Molecule
Protein (1 molecule)
Choline Kinase Alpha(Gene symbol: CHKA)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB