1gmy

==CATHEPSIN B COMPLEXED WITH DIPEPTIDYL NITRILE INHIBITOR==

<StructureSection load='1gmy' size='340' side='right' caption='[[1gmy]], [[Resolution|resolution]] 1.90&Aring;' scene=''>

<table><tr><td colspan='2'>[[1gmy]] is a 3 chain structure with 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1GMY FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1csb|1csb]], [[1huc|1huc]], [[1pbh|1pbh]], [[2pbh|2pbh]], [[3pbh|3pbh]]</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></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=1gmy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gmy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1gmy RCSB], [http://www.ebi.ac.uk/pdbsum/1gmy PDBsum]</span></td></tr>

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gm/1gmy_consurf.spt"</scriptWhenChecked>

</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/chain_selection.php?pdb_ID=2ata ConSurf].

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== Publication Abstract from PubMed ==

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.

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<ref>PMID:11741472</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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*[[Cathepsin|Cathepsin]]

[[Category: Cathepsin B]]

[[Category: Bohacek, R S]]

[[Category: Capparelli, M P]]

[[Category: Clark, K L]]

[[Category: Coppa, D E]]

[[Category: Cowen, S D]]

[[Category: Doughty, J R]]

[[Category: Du, Z]]

[[Category: Duzer, J H.Van]]

[[Category: Fang, Z]]

[[Category: Farley, D L]]

[[Category: Fitt, J J]]

[[Category: Goldberg, R L]]

[[Category: Goldstein, R]]

[[Category: Greenspan, P D]]

[[Category: Knap, A K]]

[[Category: Macchia, W]]

[[Category: Mcquire, L W]]

[[Category: Tommasi, R A]]

[[Category: Wigg, A M]]

[[Category: Zhou, H]]

[[Category: Zhu, L]]

[[Category: Cathepsin b]]

[[Category: Thiol protease]]