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1gmy

From Proteopedia

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[[Image:1gmy.gif|left|200px]]
 
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==Cathepsin B complexed with dipeptidyl nitrile inhibitor==
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The line below this paragraph, containing "STRUCTURE_1gmy", creates the "Structure Box" on the page.
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<StructureSection load='1gmy' size='340' side='right'caption='[[1gmy]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1gmy]] is a 3 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=1GMY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GMY FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr>
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{{STRUCTURE_1gmy| PDB=1gmy | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1gmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gmy OCA], [https://pdbe.org/1gmy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gmy RCSB], [https://www.ebi.ac.uk/pdbsum/1gmy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gmy ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CATB_HUMAN CATB_HUMAN] Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gm/1gmy_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1gmy ConSurf].
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<div style="clear:both"></div>
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'''CATHEPSIN B COMPLEXED WITH DIPEPTIDYL NITRILE INHIBITOR'''
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==See Also==
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*[[Cathepsin 3D structures|Cathepsin 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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.
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==About this Structure==
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1GMY 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=1GMY OCA].
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/11741472 11741472]
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[[Category: Cathepsin B]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Bohacek, R S.]]
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[[Category: Bohacek RS]]
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[[Category: Capparelli, M P.]]
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[[Category: Capparelli MP]]
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[[Category: Clark, K L.]]
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[[Category: Clark KL]]
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[[Category: Coppa, D E.]]
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[[Category: Coppa DE]]
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[[Category: Cowen, S D.]]
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[[Category: Cowen SD]]
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[[Category: Doughty, J R.]]
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[[Category: Doughty JR]]
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[[Category: Du, Z.]]
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[[Category: Du Z]]
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[[Category: Duzer, J H.Van.]]
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[[Category: Fang Z]]
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[[Category: Fang, Z.]]
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[[Category: Farley DL]]
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[[Category: Farley, D L.]]
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[[Category: Fitt JJ]]
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[[Category: Fitt, J J.]]
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[[Category: Goldberg RL]]
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[[Category: Goldberg, R L.]]
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[[Category: Goldstein R]]
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[[Category: Goldstein, R.]]
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[[Category: Greenspan PD]]
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[[Category: Greenspan, P D.]]
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[[Category: Knap AK]]
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[[Category: Knap, A K.]]
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[[Category: Macchia W]]
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[[Category: Macchia, W.]]
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[[Category: McQuire LW]]
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[[Category: Mcquire, L W.]]
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[[Category: Tommasi RA]]
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[[Category: Tommasi, R A.]]
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[[Category: Wigg AM]]
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[[Category: Wigg, A M.]]
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[[Category: Zhou H]]
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[[Category: Zhou, H.]]
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[[Category: Zhu L]]
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[[Category: Zhu, L.]]
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[[Category: Van Duzer JH]]
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[[Category: Cathepsin b]]
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[[Category: Covalent complex]]
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[[Category: Hydrolase]]
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[[Category: 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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Current revision

Cathepsin B complexed with dipeptidyl nitrile inhibitor

PDB ID 1gmy

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