2HH5

Crystal Structure of Cathepsin S in complex with a Zinc mediated non-covalent arylaminoethyl amide

Summary for 2HH5

• Entry DOI: 10.2210/pdb2hh5/pdb
• Related: 2F1G 2HHN
• Descriptor: Cathepsin S, ZINC ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: cathepsin s, noncovalent, inhibition, zinc, arylaminoethyl-amides, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P25774
• Total number of polymer chains: 2
• Total formula weight: 50391.34

Authors

Spraggon, G.,Hornsby, M.,Lesley, S.A.,Tully, D.C.,Harris, J.L.,Karenewsky, D.S. (deposition date: 2006-06-27, release date: 2006-08-15, Last modification date: 2023-08-30)

Primary citation

Tully, D.C.,Liu, H.,Chatterjee, A.K.,Alper, P.B.,Epple, R.,Williams, J.A.,Roberts, M.J.,Woodmansee, D.H.,Masick, B.T.,Tumanut, C.,Li, J.,Spraggon, G.,Hornsby, M.,Chang, J.,Tuntland, T.,Hollenbeck, T.,Gordon, P.,Harris, J.L.,Karanewsky, D.S.
Synthesis and SAR of arylaminoethyl amides as noncovalent inhibitors of cathepsin S: P3 cyclic ethers.
Bioorg.Med.Chem.Lett., 16:5112-5117, 2006

PubMed Abstract: The synthesis and structure-activity relationship of a series of arylaminoethyl amide cathepsin S inhibitors are reported. Optimization of P3 and P2 groups to improve overall physicochemical properties resulted in significant improvements in oral bioavailability over early lead compounds. An X-ray structure of compound 37 bound to the active site of cathepsin S is also reported.

PubMed: 16876402
DOI: 10.1016/j.bmcl.2006.07.033

Experimental method

X-RAY DIFFRACTION (1.8 Å)