2XNN

Structure of Nek2 bound to CCT242430

2XNN の概要

• エントリーDOI: 10.2210/pdb2xnn/pdb
• 関連するPDBエントリー: 2JAV 2W5A 2W5B 2W5H 2WQO 2XK3 2XK4 2XK6 2XK7 2XK8 2XKC 2XKD 2XKE 2XKF 2XNM 2XNO 2XNP
• 分子名称: SERINE/THREONINE-PROTEIN KINASE NEK2, 5-(1H-benzimidazol-1-yl)-3-{(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy}thiophene-2-carboxamide, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: transferase, centrosome, mitosis, cell cycle
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus. Isoform 1: Nucleus, nucleolus. Isoform 2: Cytoplasm: P51955
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33643.58

構造登録者

Mas-Droux, C.,Bayliss, R. (登録日: 2010-08-05, 公開日: 2011-03-30, 最終更新日: 2023-12-20)

主引用文献

Solanki, S.,Innocenti, P.,Mas-Droux, C.,Boxall, K.,Barillari, C.,Van Montfort, R.L.,Aherne, G.W.,Bayliss, R.,Hoelder, S.
Benzimidazole Inhibitors Induce a Dfg-Out Conformation of Never in Mitosis Gene A-Related Kinase 2 (Nek2) without Binding to the Back Pocket and Reveal a Nonlinear Structure-Activity Relationship.
J.Med.Chem., 54:1626-, 2011

PubMed Abstract: We describe herein the structure-activity relationship (SAR) and cocrystal structures of a series of Nek2 inhibitors derived from the published polo-like kinase 1 (Plk1) inhibitor (R)-1. Our studies reveal a nonlinear SAR for Nek2 and our cocrystal structures show that compounds in this series bind to a DFG-out conformation of Nek2 without extending into the enlarged back pocket commonly found in this conformation. These observations were further investigated, and structure-based design led to Nek2 inhibitors derived from (R)-1 with more than a hundred-fold selectivity against Plk1.

PubMed: 21366329
DOI: 10.1021/JM1011726

実験手法

X-RAY DIFFRACTION (2.5 Å)