2op3
From Proteopedia
(New page: 200px<br /> <applet load="2op3" size="450" color="white" frame="true" align="right" spinBox="true" caption="2op3, resolution 1.60Å" /> '''The structure of ca...) |
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| - | [[Image:2op3. | + | [[Image:2op3.jpg|left|200px]]<br /><applet load="2op3" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2op3, resolution 1.60Å" /> | caption="2op3, resolution 1.60Å" /> | ||
'''The structure of cathepsin S with a novel 2-arylphenoxyacetaldehyde inhibitor derived by the Substrate Activity Screening (SAS) method'''<br /> | '''The structure of cathepsin S with a novel 2-arylphenoxyacetaldehyde inhibitor derived by the Substrate Activity Screening (SAS) method'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2OP3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4, TF5 and PEU as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cathepsin_S Cathepsin S], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.27 3.4.22.27] Full crystallographic information is available from [http:// | + | 2OP3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=TF5:'>TF5</scene> and <scene name='pdbligand=PEU:'>PEU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cathepsin_S Cathepsin S], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.27 3.4.22.27] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OP3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: substrate activity screening]] | [[Category: substrate activity screening]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:56:50 2008'' |
Revision as of 11:56, 23 January 2008
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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 muM 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 with , and as ligands. Active as Cathepsin S, with EC number 3.4.22.27 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 1;. PMID:17469812
Page seeded by OCA on Wed Jan 23 13:56:50 2008
Categories: Cathepsin S | Homo sapiens | Single protein | Ellman, J.A. | Hornsby, M. | Inagaki, H. | Lesley, S.A. | Spraggon, G. | Tsuruoka, H. | PEU | SO4 | TF5 | Cathepsin s | Nonpeptidic | Substrate activity screening
