1kyn

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KTP:(2-NAPHTHALEN-2-YL-1-NAPHTHALEN-1-YL-2-OXO-ETHYL)-PHOSPHONIC+ACID'>KTP</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cathepsin_G Cathepsin G], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.20 3.4.21.20] </span></td></tr>

[[https://www.uniprot.org/uniprot/CATG_HUMAN CATG_HUMAN]] Serine protease with trypsin- and chymotrypsin-like specificity. Cleaves complement C3. Has antibacterial activity against the Gram-negative bacterium P.aeruginosa, antibacterial activity is inhibited by LPS from P.aeruginosa, Z-Gly-Leu-Phe-CH2Cl and phenylmethylsulfonyl fluoride.<ref>PMID:8194606</ref> <ref>PMID:1861080</ref> <ref>PMID:1937776</ref>

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

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.

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<ref>PMID:11942800</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 1kyn" style="background-color:#fffaf0;"></div>

[[Category: Cathepsin G]]

[[Category: Almond, H R]]

[[Category: Andrade-Gordon, P]]

[[Category: Chattopadhyay, D]]

[[Category: Corcoran, T W]]

[[Category: Garavilla, L De]]

[[Category: Greco, M N]]

[[Category: Hawkins, M J]]

[[Category: Kauffman, J A]]

[[Category: Maryanoff, B E]]

[[Category: Powell, E T]]

[[Category: Recacha, R]]

[[Category: Serine protease]]