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1kyn

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Revision as of 23:08, 10 September 2015

Cathepsin-G

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:
Activity:	Cathepsin G, with EC number 3.4.21.20
Resources:	FirstGlance, OCA, PDBe, 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.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Avril LE, Di Martino-Ferrer M, Pignede G, Seman M, Gauthier F. Identification of the U-937 membrane-associated proteinase interacting with the V3 loop of HIV-1 gp120 as cathepsin G. FEBS Lett. 1994 May 23;345(1):81-6. PMID:8194606
↑ Maison CM, Villiers CL, Colomb MG. Proteolysis of C3 on U937 cell plasma membranes. Purification of cathepsin G. J Immunol. 1991 Aug 1;147(3):921-6. PMID:1861080
↑ Wasiluk KR, Skubitz KM, Gray BH. Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa. Infect Immun. 1991 Nov;59(11):4193-200. PMID:1937776
↑ 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. Nonpeptide inhibitors of cathepsin G: optimization of a novel beta-ketophosphonic acid lead by structure-based drug design. J Am Chem Soc. 2002 Apr 17;124(15):3810-1. PMID:11942800

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1kyn"

@@ Line 5: / Line 5: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[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></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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.rcsb.org/pdb/explore.do?structureId=1kyn RCSB], [http://www.ebi.ac.uk/pdbsum/1kyn PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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://pdbe.org/1kyn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1kyn RCSB], [http://www.ebi.ac.uk/pdbsum/1kyn PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1kyn" style="background-color:#fffaf0;"></div>
 ==See Also==

1kyn

From Proteopedia

Revision as of 23:08, 10 September 2015

Cathepsin-G

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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