4H71

Human Plk1-PBD in complex with Poloxime ((E)-4-(hydroxyimino)-2-isopropyl-5-methylcyclohexa-2,5-dienone)

「3MHN」から置き換えられました

4H71 の概要

• エントリーDOI: 10.2210/pdb4h71/pdb
• 関連するPDBエントリー: 4H5X 4H70
• 分子名称: Serine/threonine-protein kinase PLK1, GLYCEROL, 2-methyl-5-(1-methylethyl)cyclohexa-2,5-diene-1,4-dione 1-oxime, ... (4 entities in total)
• 機能のキーワード: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P53350
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55360.06

構造登録者

Yin, Z.,Rehse, P.H. (登録日: 2012-09-19, 公開日: 2012-10-03, 最終更新日: 2023-11-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.93 Å)