4D2P

Structure of MELK in complex with inhibitors

4D2P の概要

• エントリーDOI: 10.2210/pdb4d2p/pdb
• 関連するPDBエントリー: 4D2T 4D2V 4D2W
• 分子名称: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE, 7-({4-[(3-hydroxy-5-methoxyphenyl)amino]benzoyl}amino)-1,2,3,4-tetrahydroisoquinolinium (3 entities in total)
• 機能のキーワード: transferase, fragment sterbased drug design, kinase
• 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: 4
• 化学式量合計: 165066.91

構造登録者

Johnson, C.N.,Berdini, V.,Beke, L.,Bonnet, P.,Brehmer, D.,Coyle, J.E.,Day, P.J.,Frederickson, M.,Freyne, E.J.E.,Gilissen, R.A.H.J.,Hamlett, C.C.F.,Howard, S.,Meerpoel, L.,McMenamin, R.,Patel, S.,Rees, D.C.,Sharff, A.,Sommen, F.,Wu, T.,Linders, J.T.M. (登録日: 2014-05-12, 公開日: 2014-10-08, 最終更新日: 2024-05-08)

主引用文献

Johnson, C.N.,Berdini, V.,Beke, L.,Bonnet, P.,Brehmer, D.,Coyle, J.E.,Day, P.J.,Frederickson, M.,Freyne, E.J.E.,Gilissen, R.A.H.J.,Hamlett, C.C.F.,Howard, S.,Meerpoel, L.,Mcmenamin, R.,Patel, S.,Rees, D.C.,Sharff, A.,Sommen, F.,Wu, T.,Linders, J.T.M.
Fragment-Based Discovery of Type I Inhibitors of Maternal Embryonic Leucine Zipper Kinase
Acs Med.Chem.Lett., 6:25-, 2015

PubMed Abstract: Fragment-based drug design was successfully applied to maternal embryonic leucine zipper kinase (MELK). A low affinity (160 μM) fragment hit was identified, which bound to the hinge region with an atypical binding mode, and this was optimized using structure-based design into a low-nanomolar and cell-penetrant inhibitor, with a good selectivity profile, suitable for use as a chemical probe for elucidation of MELK biology.

PubMed: 25589925
DOI: 10.1021/ML5001245

実験手法

X-RAY DIFFRACTION (2.55 Å)