Structural highlights
Function
[CATS_HUMAN] Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L and cathepsin N.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The substrate activity screening (SAS) method, a substrate-based fragment identification and optimization method for the development of enzyme inhibitors, was previously applied to cathepsin S to obtain a novel (2-arylphenoxy)acetaldehyde inhibitor, 2, with a 0.49 microM Ki value (Wood, W. J. L.; Patterson, A. W.; Tsuruoka, H.; Jain, R. K.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 15521-15527). In this paper we disclose the X-ray structure of a complex between cathepsin S and inhibitor 2 which reveals an unprecedented binding mode. On the basis of this structure, additional 2-biaryloxy substrates with greatly increased cleavage efficiency were designed. Conversion of the optimized substrates to the corresponding aldehyde inhibitors yielded a low molecular weight (304 Daltons) and potent (9.6 nM) cathepsin S inhibitor that showed from 100- to >1000-fold selectivity relative to cathepsins B, L, and K.
Characterization and optimization of selective, nonpeptidic inhibitors of cathepsin S with an unprecedented binding mode.,Inagaki H, Tsuruoka H, Hornsby M, Lesley SA, Spraggon G, Ellman JA J Med Chem. 2007 May 31;50(11):2693-9. Epub 2007 May 1. PMID:17469812[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Inagaki H, Tsuruoka H, Hornsby M, Lesley SA, Spraggon G, Ellman JA. Characterization and optimization of selective, nonpeptidic inhibitors of cathepsin S with an unprecedented binding mode. J Med Chem. 2007 May 31;50(11):2693-9. Epub 2007 May 1. PMID:17469812 doi:http://dx.doi.org/10.1021/jm070111+
