5MAG

Crystal structure of MELK in complex with an inhibitor

5MAG の概要

• エントリーDOI: 10.2210/pdb5mag/pdb
• 分子名称: Maternal embryonic leucine zipper kinase, PF-3758309, DIMETHYL SULFOXIDE, ... (5 entities in total)
• 機能のキーワード: kinase, inhibitor, complex, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane ; Peripheral membrane protein : Q14680
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40881.39

構造登録者

Canevari, G.,Re Depaolini, S.,Casale, E.,Felder, E.,Kuster, B.,Heinzlmeir, S. (登録日: 2016-11-03, 公開日: 2017-12-06, 最終更新日: 2024-11-06)

主引用文献

Klaeger, S.,Heinzlmeir, S.,Wilhelm, M.,Polzer, H.,Vick, B.,Koenig, P.A.,Reinecke, M.,Ruprecht, B.,Petzoldt, S.,Meng, C.,Zecha, J.,Reiter, K.,Qiao, H.,Helm, D.,Koch, H.,Schoof, M.,Canevari, G.,Casale, E.,Depaolini, S.R.,Feuchtinger, A.,Wu, Z.,Schmidt, T.,Rueckert, L.,Becker, W.,Huenges, J.,Garz, A.K.,Gohlke, B.O.,Zolg, D.P.,Kayser, G.,Vooder, T.,Preissner, R.,Hahne, H.,Tonisson, N.,Kramer, K.,Gotze, K.,Bassermann, F.,Schlegl, J.,Ehrlich, H.C.,Aiche, S.,Walch, A.,Greif, P.A.,Schneider, S.,Felder, E.R.,Ruland, J.,Medard, G.,Jeremias, I.,Spiekermann, K.,Kuster, B.
The target landscape of clinical kinase drugs.
Science, 358:-, 2017

PubMed Abstract: Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.

PubMed: 29191878
DOI: 10.1126/science.aan4368

実験手法

X-RAY DIFFRACTION (2.35 Å)