1kyn
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1kyn.jpg|left|200px]] | + | [[Image:1kyn.jpg|left|200px]] |
| - | + | ||
| - | '''Cathepsin-G''' | + | {{Structure |
| + | |PDB= 1kyn |SIZE=350|CAPTION= <scene name='initialview01'>1kyn</scene>, resolution 3.50Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=KTP:(2-NAPHTHALEN-2-YL-1-NAPHTHALEN-1-YL-2-OXO-ETHYL)-PHOSPHONIC ACID'>KTP</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Cathepsin_G Cathepsin G], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.20 3.4.21.20] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Cathepsin-G''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1KYN is a [ | + | 1KYN is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KYN OCA]. |
==Reference== | ==Reference== | ||
| - | Nonpeptide inhibitors of cathepsin G: optimization of a novel beta-ketophosphonic acid lead by structure-based drug design., Greco MN, Hawkins MJ, Powell ET, Almond HR Jr, Corcoran TW, de Garavilla L, Kauffman JA, Recacha R, Chattopadhyay D, Andrade-Gordon P, Maryanoff BE, J Am Chem Soc. 2002 Apr 17;124(15):3810-1. PMID:[http:// | + | Nonpeptide inhibitors of cathepsin G: optimization of a novel beta-ketophosphonic acid lead by structure-based drug design., Greco MN, Hawkins MJ, Powell ET, Almond HR Jr, Corcoran TW, de Garavilla L, Kauffman JA, Recacha R, Chattopadhyay D, Andrade-Gordon P, Maryanoff BE, J Am Chem Soc. 2002 Apr 17;124(15):3810-1. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11942800 11942800] |
[[Category: Cathepsin G]] | [[Category: Cathepsin G]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| Line 28: | Line 37: | ||
[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:23:57 2008'' |
Revision as of 10:23, 20 March 2008
| |||||||
| , resolution 3.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Cathepsin G, with EC number 3.4.21.20 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Cathepsin-G
Overview
The serine protease cathepsin G (EC 3.4.21.20; Cat G), which is stored in the azurophilic granules of neutrophils (polymorphonuclear leukocytes) and released on degranulation, has been implicated in various pathological conditions associated with inflammation. By employing high-throughput screening, we identified beta-ketophosphonic acid 1 as a moderate inhibitor of Cat G (IC(50) = 4.1 microM). We were fortunate to obtain a cocrystal of 1 with Cat G and solve its structure by X-ray crystallography (3.5 A). Structural details from the X-ray analysis of 1.Cat G served as a platform for optimization of this lead compound by structure-based drug design. With the aid of molecular modeling, substituents were attached to the 3-position of the 2-naphthyl ring of 1, which occupies the S1 pocket of Cat G, to provide an extension into the hydrophobic S3 region. Thus, we arrived at analogue 7 with an 80-fold potency improvement over 1 (IC(50) = 53 nM). From these results, it is evident that the beta-ketophosphonic acid unit can form the basis for a novel class of serine protease inhibitors.
About this Structure
1KYN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Nonpeptide inhibitors of cathepsin G: optimization of a novel beta-ketophosphonic acid lead by structure-based drug design., Greco MN, Hawkins MJ, Powell ET, Almond HR Jr, Corcoran TW, de Garavilla L, Kauffman JA, Recacha R, Chattopadhyay D, Andrade-Gordon P, Maryanoff BE, J Am Chem Soc. 2002 Apr 17;124(15):3810-1. PMID:11942800
Page seeded by OCA on Thu Mar 20 12:23:57 2008
