7NB2

Crystal structure of human choline alpha in complex with an inhibitor

これはPDB形式変換不可エントリーです。

7NB2 の概要

• エントリーDOI: 10.2210/pdb7nb2/pdb
• 分子名称: Choline kinase alpha, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, 4-(6-azanyl-2-chloranyl-purin-9-yl)-~{N}-(4-methyl-1,3-thiazol-2-yl)cyclohexane-1-carboxamide, ... (5 entities in total)
• 機能のキーワード: transferase, phosphatidylcholine, inhibitor complex
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 91570.30

構造登録者

Casale, E.,Fasolini, M. (登録日: 2021-01-25, 公開日: 2021-10-13, 最終更新日: 2024-01-31)

主引用文献

Quartieri, F.,Nesi, M.,Avanzi, N.R.,Borghi, D.,Casale, E.,Corti, E.,Cucchi, U.,Donati, D.,Fasolini, M.,Felder, E.R.,Galvani, A.,Giorgini, M.L.,Lomolino, A.,Menichincheri, M.,Orrenius, C.,Perrera, C.,Re Depaolini, S.,Riccardi-Sirtori, F.,Salsi, E.,Isacchi, A.,Gnocchi, P.
Identification of unprecedented ATP-competitive choline kinase inhibitors.
Bioorg.Med.Chem.Lett., 51:128310-128310, 2021

PubMed Abstract: In this article we describe the identification of unprecedented ATP-competitive ChoKα inhibitors starting from initial hit NMS-P830 that binds to ChoKα in an ATP concentration-dependent manner. This result is confirmed by the co-crystal structure of NMS-P830 in complex with Δ75-ChoKα. NMS-P830 is able to inhibit ChoKα in cells resulting in the reduction of intracellular phosphocholine formation. A structure-based medicinal chemistry program resulted in the identification of selective compounds that have good biochemical activity, solubility and metabolic stability and are suitable for further optimization. The ChoKα inhibitors disclosed in this article demonstrate for the first time the possibility to inhibit ChoKα with ATP-competitive compounds.

PubMed: 34416377
DOI: 10.1016/j.bmcl.2021.128310

実験手法

X-RAY DIFFRACTION (2.4 Å)