4BKY

Crystal structure of unphosphorylated Maternal Embryonic Leucine zipper Kinase (MELK) in complex with pyrrolopyrazole inhibitor

4BKY の概要

• エントリーDOI: 10.2210/pdb4bky/pdb
• 関連するPDBエントリー: 4BKZ 4BL1
• 分子名称: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE, 3'-{[(4-bromo-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-N-[(1S)-1-phenyl-2-(pyrrolidin-1-yl)ethyl]-1',4'-dihydro-5'H-spiro[cyclopropane-1,6'-pyrrolo[3,4-c]pyrazole]-5'-carboxamide, UNKNOWN ATOM OR ION, ... (4 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40773.00

構造登録者

Canevari, G.,Re Depaolini, S.,Cucchi, U.,Forte, B.,Carpinelli, P.,Bertrand, J.A. (登録日: 2013-04-30, 公開日: 2013-08-21, 最終更新日: 2023-12-20)

主引用文献

Canevari, G.,Re Depaolini, S.,Cucchi, U.,Bertrand, J.A.,Casale, E.,Perrera, C.,Forte, B.,Carpinelli, P.,Felder, E.R.
Structural Insight Into Maternal Embryonic Leucine Zipper Kinase (Melk) Conformation and Inhibition Towards Structure- Based Drug Design.
Biochemistry, 52:6380-, 2013

PubMed Abstract: Maternal embryonic leucine zipper kinase (MELK) is upregulated in several types of tumor, including breast, prostate, and brain tumors. Its expression is generally associated with cell survival, cell proliferation, and resistance to apoptosis. Therefore, the potential of MELK inhibitors as therapeutic agents is recently attracting considerable interest. Here we report the first structures of MELK in complex with AMP-PNP and with nanomolar inhibitors. Our studies shed light on the role of the MELK UBA domain, provide a characterization of the kinase active site, and identify key residues for achieving high potency, laying the groundwork for structure-based drug design efforts.

PubMed: 23914841
DOI: 10.1021/BI4005864

実験手法

X-RAY DIFFRACTION (1.83 Å)