1kyn
From Proteopedia
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{{Structure | {{Structure | ||
|PDB= 1kyn |SIZE=350|CAPTION= <scene name='initialview01'>1kyn</scene>, resolution 3.50Å | |PDB= 1kyn |SIZE=350|CAPTION= <scene name='initialview01'>1kyn</scene>, resolution 3.50Å | ||
| - | |SITE= | + | |SITE= <scene name='pdbsite=AC1:Ktp+Binding+Site+For+Residue+A+601'>AC1</scene> and <scene name='pdbsite=AC2:Ktp+Binding+Site+For+Residue+B+701'>AC2</scene> |
|LIGAND= <scene name='pdbligand=KTP:(2-NAPHTHALEN-2-YL-1-NAPHTHALEN-1-YL-2-OXO-ETHYL)-PHOSPHONIC+ACID'>KTP</scene> | |LIGAND= <scene name='pdbligand=KTP:(2-NAPHTHALEN-2-YL-1-NAPHTHALEN-1-YL-2-OXO-ETHYL)-PHOSPHONIC+ACID'>KTP</scene> | ||
|ACTIVITY= <span class='plainlinks'>[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] </span> | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
| - | |DOMAIN= | + | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd00190 Tryp_SPc]</span> |
|RELATEDENTRY= | |RELATEDENTRY= | ||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1kyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kyn OCA], [http://www.ebi.ac.uk/pdbsum/1kyn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1kyn RCSB]</span> | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1kyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kyn OCA], [http://www.ebi.ac.uk/pdbsum/1kyn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1kyn RCSB]</span> | ||
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[[Category: Powell, E T.]] | [[Category: Powell, E T.]] | ||
[[Category: Recacha, R.]] | [[Category: Recacha, R.]] | ||
| + | [[Category: hydrolase]] | ||
[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 2 11:31:27 2008'' |
Revision as of 08:31, 2 April 2008
| |||||||
| , resolution 3.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | |||||||
| Activity: | Cathepsin G, with EC number 3.4.21.20 | ||||||
| Domains: | Tryp_SPc | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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
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