5QBV

Crystal structure of human Cathepsin-S with bound ligand

「3MPF」から置き換えられました

5QBV の概要

• エントリーDOI: 10.2210/pdb5qbv/pdb
• Group deposition: Ligand binding to Cathepsin S (G_1002040)
• 分子名称: Cathepsin S, N-[2-chloro-5-(1-{3-[4-(6-chloro-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]propyl}-6-oxo-1,6-dihydropyridazin-3-yl)benzyl]benzamide (3 entities in total)
• 機能のキーワード: d3r, cathepsin s, ligand docking, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50324.10

構造登録者

Bembenek, S.D.,Ameriks, M.K.,Mirzadegan, T.,Yang, H.,Shao, C.,Burley, S.K. (登録日: 2017-08-04, 公開日: 2017-12-20, 最終更新日: 2024-10-16)

主引用文献

Ameriks, M.K.,Bembenek, S.D.,Burdett, M.T.,Choong, I.C.,Edwards, J.P.,Gebauer, D.,Gu, Y.,Karlsson, L.,Purkey, H.E.,Staker, B.L.,Sun, S.,Thurmond, R.L.,Zhu, J.
Diazinones as P2 replacements for pyrazole-based cathepsin S inhibitors
Bioorg.Med.Chem.Lett., 20:4060-4064, 2010

PubMed Abstract: A pyridazin-4-one fragment 4 (hCatS IC(50)=170 microM) discovered through Tethering was modeled into cathepsin S and predicted to overlap in S2 with the tetrahydropyridinepyrazole core of a previously disclosed series of CatS inhibitors. This fragment served as a template to design pyridazin-3-one 12 (hCatS IC(50)=430 nM), which also incorporates P3 and P5 binding elements. A crystal structure of 12 bound to Cys25Ser CatS led to the synthesis of the potent diazinone isomers 22 (hCatS IC(50)=60 nM) and 27 (hCatS IC(50)=40 nM).

PubMed: 20541404
DOI: 10.1016/j.bmcl.2010.05.086

実験手法

X-RAY DIFFRACTION (1.796 Å)