2XKF

Structure of Nek2 bound to aminopyrazine compound 2

2XKF の概要

• エントリーDOI: 10.2210/pdb2xkf/pdb
• 関連するPDBエントリー: 2JAV 2W5A 2W5B 2W5H 2WQO 2XK3 2XK4 2XK6 2XK7 2XK8 2XKC 2XKD 2XKE 2XNM 2XNN 2XNO 2XNP
• 分子名称: SERINE/THREONINE-PROTEIN KINASE NEK2, 1-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]piperidine-4-carboxylic acid, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: transferase, centrosome, mitosis
• 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: 33192.71

構造登録者

Mas-Droux, C.,Bayliss, R. (登録日: 2010-07-07, 公開日: 2010-10-27, 最終更新日: 2023-12-20)

主引用文献

Whelligan, D.K.,Solanki, S.,Taylor, D.,Thomson, D.W.,Cheung, K.M.,Boxall, K.,Mas-Droux, C.,Barillari, C.,Burns, S.,Grummitt, C.G.,Collins, I.,Van Montfort, R.L.,Aherne, G.W.,Bayliss, R.,Hoelder, S.
Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.
J.Med.Chem., 53:7682-, 2010

PubMed Abstract: We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.

PubMed: 20936789
DOI: 10.1021/JM1008727

実験手法

X-RAY DIFFRACTION (2.35 Å)