3RQ7

Polo-like kinase 1 Polo box domain in complex with a C6H5(CH2)8-derivatized peptide inhibitor

3RQ7 の概要

• エントリーDOI: 10.2210/pdb3rq7/pdb
• 関連するPDBエントリー: 1Q4K 1UMW 3BZI 3C5L 3FVH 3HIK
• 関連するBIRD辞書のPRD_ID: PRD_000794
• 分子名称: Serine/threonine-protein kinase PLK1, C6H5(CH2)8-derivatized peptide inhibitor (3 entities in total)
• 機能のキーワード: phosphopeptide binding domain, 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: 28131.10

構造登録者

Liu, F.,Park, J.-E.,Qian, W.-J.,Lim, D.C.,Graber, M.,Berg, T.,Yaffe, M.B.,Lee, K.S.,Burke Jr., T.R. (登録日: 2011-04-27, 公開日: 2011-07-20, 最終更新日: 2024-10-16)

主引用文献

Liu, F.,Park, J.E.,Qian, W.J.,Lim, D.,Graber, M.,Berg, T.,Yaffe, M.B.,Lee, K.S.,Burke, T.R.
Serendipitous alkylation of a Plk1 ligand uncovers a new binding channel.
Nat.Chem.Biol., 7:595-601, 2011

PubMed Abstract: We obtained unanticipated synthetic byproducts from alkylation of the δ(1) nitrogen (N3) of the histidine imidazole ring of the polo-like kinase-1 (Plk1) polo-box domain (PBD)-binding peptide PLHSpT. For the highest-affinity byproduct, bearing a C(6)H(5)(CH(2))(8)- group, a Plk1 PBD cocrystal structure revealed a new binding channel that had previously been occluded. An N-terminal PEGylated version of this peptide containing a hydrolytically stable phosphothreonyl residue (pT) bound the Plk1 PBD with affinity equal to that of the non-PEGylated parent but showed markedly less interaction with the PBDs of the two closely related proteins Plk2 and Plk3. Treatment of cultured cells with this PEGylated peptide resulted in delocalization of Plk1 from centrosomes and kinetochores and in chromosome misalignment that effectively induced mitotic block and apoptotic cell death. This work provides insights that might advance efforts to develop Plk1 PBD-binding inhibitors as potential Plk1-specific anticancer agents.

PubMed: 21765407
DOI: 10.1038/nchembio.614

実験手法

X-RAY DIFFRACTION (1.55 Å)