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[[Image:1kyn.jpg|left|200px]]
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{{STRUCTURE_1kyn|  PDB=1kyn  |  SCENE=  }}
'''Cathepsin-G'''


==Cathepsin-G==
<StructureSection load='1kyn' size='340' side='right'caption='[[1kyn]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1kyn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KYN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1kyn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kyn OCA], [https://pdbe.org/1kyn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kyn RCSB], [https://www.ebi.ac.uk/pdbsum/1kyn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kyn ProSAT]</span></td></tr>
</table>
== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ky/1kyn_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1kyn ConSurf].
<div style="clear:both"></div>
<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.


==Overview==
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>
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==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1KYN is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KYN OCA].
</div>
<div class="pdbe-citations 1kyn" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://www.ncbi.nlm.nih.gov/pubmed/11942800 11942800]
*[[Cathepsin 3D structures|Cathepsin 3D structures]]
[[Category: Cathepsin G]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Andrade-Gordon, P.]]
[[Category: Almond Jr HR]]
[[Category: Chattopadhyay, D.]]
[[Category: Andrade-Gordon P]]
[[Category: Corcoran, T W.]]
[[Category: Chattopadhyay D]]
[[Category: Garavilla, L De.]]
[[Category: Corcoran TW]]
[[Category: Greco, M N.]]
[[Category: De Garavilla L]]
[[Category: Hawkins, M J.]]
[[Category: Greco MN]]
[[Category: Jr., H R.Almond.]]
[[Category: Hawkins MJ]]
[[Category: Kauffman, J A.]]
[[Category: Kauffman JA]]
[[Category: Maryanoff, B E.]]
[[Category: Maryanoff BE]]
[[Category: Powell, E T.]]
[[Category: Powell ET]]
[[Category: Recacha, R.]]
[[Category: Recacha R]]
[[Category: Hydrolase]]
[[Category: Serine protease]]
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