3HIK

Structure of human Plk1-PBD in complex with PLHSpT

3HIK の概要

• エントリーDOI: 10.2210/pdb3hik/pdb
• 分子名称: Serine/threonine-protein kinase PLK1, Pentamer phosphopeptide, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: kinase, serine/threonine protein kinase, cell cycle, localization, atp-binding, cell division, mitosis, nucleotide-binding, nucleus, phosphoprotein, serine/threonine-protein kinase, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 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: 28179.00

構造登録者

Wlodawer, A.,Moulaei, T. (登録日: 2009-05-20, 公開日: 2009-06-09, 最終更新日: 2024-10-30)

主引用文献

Yun, S.M.,Moulaei, T.,Lim, D.,Bang, J.K.,Park, J.E.,Shenoy, S.R.,Liu, F.,Kang, Y.H.,Liao, C.,Soung, N.K.,Lee, S.,Yoon, D.Y.,Lim, Y.,Lee, D.H.,Otaka, A.,Appella, E.,McMahon, J.B.,Nicklaus, M.C.,Burke, T.R.,Yaffe, M.B.,Wlodawer, A.,Lee, K.S.
Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1.
Nat.Struct.Mol.Biol., 16:876-882, 2009

PubMed Abstract: Polo-like kinase-1 (Plk1) has a pivotal role in cell proliferation and is considered a potential target for anticancer therapy. The noncatalytic polo-box domain (PBD) of Plk1 forms a phosphoepitope binding module for protein-protein interaction. Here, we report the identification of minimal phosphopeptides that specifically interact with the PBD of human PLK1, but not those of the closely related PLK2 and PLK3. Comparative binding studies and analyses of crystal structures of the PLK1 PBD in complex with the minimal phosphopeptides revealed that the C-terminal SpT dipeptide functions as a high-affinity anchor, whereas the N-terminal residues are crucial for providing specificity and affinity to the interaction. Inhibition of the PLK1 PBD by phosphothreonine mimetic peptides was sufficient to induce mitotic arrest and apoptotic cell death. The mode of interaction between the minimal peptide and PBD may provide a template for designing therapeutic agents that target PLK1.

PubMed: 19597481
DOI: 10.1038/nsmb.1628

実験手法

X-RAY DIFFRACTION (1.77 Å)