4H5X

human Plk1-PBD with a glycerol bound at the phophopeptide binding site

Replaces:  3MHQ

Summary for 4H5X

• Entry DOI: 10.2210/pdb4h5x/pdb
• Related: 4H70 4H71
• Descriptor: Serine/threonine-protein kinase PLK1, GLYCEROL (3 entities in total)
• Functional Keywords: kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P53350
• Total number of polymer chains: 2
• Total formula weight: 55180.84

Authors

Yin, Z.,Rehse, P.H. (deposition date: 2012-09-19, release date: 2012-10-03, Last modification date: 2023-11-08)

Primary citation

Yin, Z.,Song, Y.,Rehse, P.H.
Thymoquinone Blocks pSer/pThr Recognition by Plk1 Polo-Box Domain As a Phosphate Mimic
Acs Chem.Biol., 8:303-308, 2013

PubMed Abstract: 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-π 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.

PubMed: 23135290
DOI: 10.1021/cb3004379

Experimental method

X-RAY DIFFRACTION (1.95 Å)