1gmy

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[[Image:1gmy.gif|left|200px]]
[[Image:1gmy.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1gmy |SIZE=350|CAPTION= <scene name='initialview01'>1gmy</scene>, resolution 1.9&Aring;
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The line below this paragraph, containing "STRUCTURE_1gmy", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=ACT:Forms+Thioimidate+Bond+w.+Inhibitor'>ACT</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=AEM:2-AMINOETHANIMIDIC+ACID'>AEM</scene>, <scene name='pdbligand=APD:3-METHYLPHENYLALANINE'>APD</scene>, <scene name='pdbligand=DFA:DIPHENYLACETIC+ACID'>DFA</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_B Cathepsin B], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.1 3.4.22.1] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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|DOMAIN=
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{{STRUCTURE_1gmy| PDB=1gmy | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gmy OCA], [http://www.ebi.ac.uk/pdbsum/1gmy PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gmy RCSB]</span>
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}}
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'''CATHEPSIN B COMPLEXED WITH DIPEPTIDYL NITRILE INHIBITOR'''
'''CATHEPSIN B COMPLEXED WITH DIPEPTIDYL NITRILE INHIBITOR'''
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[[Category: Zhou, H.]]
[[Category: Zhou, H.]]
[[Category: Zhu, L.]]
[[Category: Zhu, L.]]
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[[Category: cathepsin b]]
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[[Category: Cathepsin b]]
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[[Category: covalent complex]]
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[[Category: Covalent complex]]
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[[Category: hydrolase]]
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[[Category: Hydrolase]]
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[[Category: protease]]
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[[Category: Protease]]
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[[Category: thiol protease]]
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[[Category: Thiol protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:45:58 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:47:14 2008''
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Revision as of 14:46, 2 May 2008

Image:1gmy.gif

Template:STRUCTURE 1gmy

CATHEPSIN B COMPLEXED WITH DIPEPTIDYL NITRILE INHIBITOR


Overview

Cathepsin B is a member of the papain superfamily of cysteine proteases and has been implicated in the pathology of numerous diseases, including arthritis and cancer. As part of an effort to identify potent, reversible inhibitors of this protease, we examined a series of dipeptidyl nitriles, starting with the previously reported Cbz-Phe-NH-CH(2)CN (19, IC(50) = 62 microM). High-resolution X-ray crystallographic data and molecular modeling were used to optimize the P(1), P(2), and P(3) substituents of this template. Cathepsin B is unique in its class in that it contains a carboxylate recognition site in the S(2)' pocket of the active site. Inhibitor potency and selectivity were enhanced by tethering a carboxylate functionality from the carbon alpha to the nitrile to interact with this region of the enzyme. This resulted in the identification of compound 10, a 7 nM inhibitor of cathepsin B, with excellent selectivity over other cysteine cathepsins.

About this Structure

1GMY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Identification of dipeptidyl nitriles as potent and selective inhibitors of cathepsin B through structure-based drug design., Greenspan PD, Clark KL, Tommasi RA, Cowen SD, McQuire LW, Farley DL, van Duzer JH, Goldberg RL, Zhou H, Du Z, Fitt JJ, Coppa DE, Fang Z, Macchia W, Zhu L, Capparelli MP, Goldstein R, Wigg AM, Doughty JR, Bohacek RS, Knap AK, J Med Chem. 2001 Dec 20;44(26):4524-34. PMID:11741472 Page seeded by OCA on Fri May 2 17:45:58 2008

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