4H5X: Human Plk1-pbd With A Glycerol Bound At The Phophopeptide Binding Site

Phosphorylation-dependent protein-protein interaction has rarely been targeted in medicinal chemistry. Thymoquinone, a naturally occurring antitumor agent, disrupts prephosphorylated substrate recognition by the polo-box domain of polo-like kinase 1, a key mitotic regulator responsible for various carcinogenesis when overexpressed. Here, crystallographic studies reveal that the phosphoserine/phosphothreonine recognition site of the polo-box domain is the binding pocket for thymoquinone and its analogue poloxime. Both small molecules displace phosphopeptides bound with the polo-box domain in a slow but noncovalent binding mode. A conserved water bridge and a cation-pi interaction were found as their competition strategy against the phosphate group. This mechanism sheds light on small-molecule intervention of phospho-recognition by the polo-box domain of polo-like kinase 1 and other phospho-binding proteins in general.
PDB ID: 4H5XDownload
MMDB ID: 103625
PDB Deposition Date: 2012/9/19
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 4H5X: monomeric; determined by author and by software (PISA)
Molecular Components in 4H5X
Label Count Molecule
Protein (1 molecule)
Serine/threonine-protein Kinase Plk1(Gene symbol: PLK1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB