2op3
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2op3.jpg|left|200px]] | [[Image:2op3.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2op3", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_2op3| PDB=2op3 | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''The structure of cathepsin S with a novel 2-arylphenoxyacetaldehyde inhibitor derived by the Substrate Activity Screening (SAS) method''' | '''The structure of cathepsin S with a novel 2-arylphenoxyacetaldehyde inhibitor derived by the Substrate Activity Screening (SAS) method''' | ||
| Line 32: | Line 29: | ||
[[Category: Spraggon, G.]] | [[Category: Spraggon, G.]] | ||
[[Category: Tsuruoka, H.]] | [[Category: Tsuruoka, H.]] | ||
| - | [[Category: | + | [[Category: Cathepsin s]] |
| - | [[Category: | + | [[Category: Nonpeptidic]] |
| - | [[Category: | + | [[Category: Substrate activity screening]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 11:22:01 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 08:22, 4 May 2008
The structure of cathepsin S with a novel 2-arylphenoxyacetaldehyde inhibitor derived by the Substrate Activity Screening (SAS) method
Overview
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.
About this Structure
2OP3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sun May 4 11:22:01 2008
