3OVX

Cathepsin S in complex with a covalent inhibitor with an aldehyde warhead

Summary for 3OVX

• Entry DOI: 10.2210/pdb3ovx/pdb
• Related: 3OVZ
• Descriptor: Cathepsin S, 2-chloro-N-[(1S)-1-formylpropyl]-3-(trifluoromethyl)benzamide, DIMETHYL SULFOXIDE, ... (4 entities in total)
• Functional Keywords: cathepsin s, hydrolase, covalent inhibitor, aldehyde warhead, ligand is covalently bound to cys25, lysosomeal protein, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P25774
• Total number of polymer chains: 2
• Total formula weight: 48905.66

Authors

Fradera, X.,van Zeeland, M.,Uitdehaag, J.C.M. (deposition date: 2010-09-17, release date: 2010-12-22, Last modification date: 2024-10-16)

Primary citation

Cai, J.,Robinson, J.,Belshaw, S.,Everett, K.,Fradera, X.,van Zeeland, M.,van Berkom, L.,van Rijnsbergen, P.,Popplestone, L.,Baugh, M.,Dempster, M.,Bruin, J.,Hamilton, W.,Kinghorn, E.,Westwood, P.,Kerr, J.,Rankovic, Z.,Arbuckle, W.,Bennett, D.J.,Jones, P.S.,Long, C.,Martin, I.,Uitdehaag, J.C.,Meulemans, T.
Trifluoromethylphenyl as P2 for ketoamide-based cathepsin S inhibitors.
Bioorg.Med.Chem.Lett., 20:6890-6894, 2010

PubMed Abstract: The trifluoromethylphenyl P2 motif from previously reported heteroarylnitrile series has been successfully applied for the design and synthesis of highly potent novel ketoamide-based cathepsin S inhibitors. The key in this process is the change of the torsion angle between the P2 phenyl ring and the attached secondary amide by adding a small Cl, F, or Me group at the 2-position.

PubMed: 21030256
DOI: 10.1016/j.bmcl.2010.10.012

Experimental method

X-RAY DIFFRACTION (1.49 Å)