1kyn

Cathepsin-G

spinqualitylabelsall models 1kyn, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1kyn is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: KTP Activity: Cathepsin G, with EC number 3.4.21.20 Resources: FirstGlance, OCA, RCSB, PDBsum Function [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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cathepsin

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