2G1Q

crystal structure of KSP in complex with inhibitor 9h

2G1Q の概要

• エントリーDOI: 10.2210/pdb2g1q/pdb
• 分子名称: Kinesin-like protein KIF11, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: ksp, ksp-inhibitor complex, cell cycle
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P52732
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83787.05

構造登録者

Yan, Y. (登録日: 2006-02-14, 公開日: 2006-10-03, 最終更新日: 2024-02-14)

主引用文献

Cox, C.D.,Torrent, M.,Breslin, M.J.,Mariano, B.J.,Whitman, D.B.,Coleman, P.J.,Buser, C.A.,Walsh, E.S.,Hamilton, K.,Schaber, M.D.,Lobell, R.B.,Tao, W.,South, V.J.,Kohl, N.E.,Yan, Y.,Kuo, L.C.,Prueksaritanont, T.,Slaughter, D.E.,Li, C.,Mahan, E.,Lu, B.,Hartman, G.D.
Kinesin spindle protein (KSP) inhibitors. Part 4: Structure-based design of 5-alkylamino-3,5-diaryl-4,5-dihydropyrazoles as potent, water-soluble inhibitors of the mitotic kinesin KSP.
Bioorg.Med.Chem.Lett., 16:3175-3179, 2006

PubMed Abstract: Molecular modeling in combination with X-ray crystallographic information was employed to identify a region of the kinesin spindle protein (KSP) binding site not fully utilized by our first generation inhibitors. We discovered that by appending a propylamine substituent at the C5 carbon of a dihydropyrazole core, we could effectively fill this unoccupied region of space and engage in a hydrogen-bonding interaction with the enzyme backbone. This change led to a second generation compound with increased potency, a 400-fold enhancement in aqueous solubility at pH 4, and improved dog pharmacokinetics relative to the first generation compound.

PubMed: 16603356
DOI: 10.1016/j.bmcl.2006.03.040

実験手法

X-RAY DIFFRACTION (2.51 Å)