Summary for 5QBY
| Entry DOI | 10.2210/pdb5qby/pdb |
| Group deposition | Ligand binding to Cathepsin S (G_1002040) |
| Descriptor | 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-dihydropyrimidin-5-yl)benzyl]-4-fluorobenzamide (3 entities in total) |
| Functional Keywords | d3r, cathepsin s, ligand docking, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 50360.08 |
| Authors | Bembenek, S.D.,Ameriks, M.K.,Mirzadegan, T.,Yang, H.,Shao, C.,Burley, S.K. (deposition date: 2017-08-04, release date: 2017-12-20, Last modification date: 2024-11-06) |
| Primary citation | 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 Cited by 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: 20541404DOI: 10.1016/j.bmcl.2010.05.086 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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