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| [[Image:1kyn.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1kyn| PDB=1kyn | SCENE= }} | | {{STRUCTURE_1kyn| PDB=1kyn | SCENE= }} |
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| '''Cathepsin-G'''
| | ===Cathepsin-G=== |
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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_11942800}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11942800 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11942800}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Hydrolase]] | | [[Category: Hydrolase]] |
| [[Category: Serine protease]] | | [[Category: Serine protease]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:19:47 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 11:18:02 2008'' |
