5O11

Crystal structure of PIM1 kinase in complex with small-molecule inhibitor

5O11 の概要

• エントリーDOI: 10.2210/pdb5o11/pdb
• 分子名称: Serine/threonine-protein kinase pim-1, 5-[(3-chlorophenyl)amino]benzo[c][2,6]naphthyridine-8-carboxylic acid, IMIDAZOLE, ... (6 entities in total)
• 機能のキーワード: kinase, cx-4945, pim1, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35172.49

構造登録者

Bogusz, J.,Dubin, G. (登録日: 2017-05-17, 公開日: 2017-11-01, 最終更新日: 2024-11-13)

主引用文献

Bogusz, J.,Zrubek, K.,Rembacz, K.P.,Grudnik, P.,Golik, P.,Romanowska, M.,Wladyka, B.,Dubin, G.
Structural analysis of PIM1 kinase complexes with ATP-competitive inhibitors.
Sci Rep, 7:13399-13399, 2017

PubMed Abstract: PIM1 is an oncogenic kinase overexpressed in a number of cancers where it correlates with poor prognosis. Several studies demonstrated that inhibition of PIM1 activity is an attractive strategy in fighting overexpressing cancers, while distinct structural features of ATP binding pocket make PIM1 an inviting target for the design of selective inhibitors. To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1. Two of the reported structures (CX-4945 and Ro-3306) explain the off-target effect on PIM1 of respectively casein kinase 2 and cyclin-dependent kinase 1 dedicated inhibitors. In turn, the structure with CX-6258 demonstrates a binding mode of a potent, selective inhibitor of PIM1, PIM2, PIM3 and Flt-3 kinases. The consequences of our findings for future inhibitor development are discussed.

PubMed: 29042609
DOI: 10.1038/s41598-017-13557-z

実験手法

X-RAY DIFFRACTION (2.4 Å)