2op3: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2op3 |SIZE=350|CAPTION= <scene name='initialview01'>2op3</scene>, resolution 1.60Å | |PDB= 2op3 |SIZE=350|CAPTION= <scene name='initialview01'>2op3</scene>, resolution 1.60Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TF5:2-[(2 | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TF5:2-[(2',3',4'-TRIFLUOROBIPHENYL-2-YL)OXY]ETHANOL'>TF5</scene> and <scene name='pdbligand=PEU:2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,62,65,68,71,74,77,80-HEPTACOSAOXADOOCTACONTAN-82-OL'>PEU</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= [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] | ||
|GENE= CATHS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CATHS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| Line 36: | Line 36: | ||
[[Category: substrate activity screening]] | [[Category: substrate activity screening]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 15:34:11 2008'' | ||
Revision as of 16:34, 23 March 2008
| |||||||
| , resolution 1.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | CATHS (Homo sapiens) | ||||||
| Activity: | Cathepsin S, with EC number 3.4.22.27 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
The structure of cathepsin S with a novel 2-arylphenoxyacetaldehyde inhibitor derived by the Substrate Activity Screening (SAS) method
OverviewOverview
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 StructureAbout this Structure
2OP3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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 Mar 23 15:34:11 2008