3i06

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{{STRUCTURE_3i06| PDB=3i06 | SCENE= }}
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==Crystal structure of cruzain covalently bound to a purine nitrile==
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===Crystal structure of cruzain covalently bound to a purine nitrile===
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<StructureSection load='3i06' size='340' side='right' caption='[[3i06]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
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{{ABSTRACT_PUBMED_19908842}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3i06]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I06 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I06 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QL2:6-[(3,5-DIFLUOROPHENYL)AMINO]-9-ETHYL-9H-PURINE-2-CARBONITRILE'>QL2</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cruzipain Cruzipain], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.51 3.4.22.51] </span></td></tr>
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<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=3i06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i06 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3i06 RCSB], [http://www.ebi.ac.uk/pdbsum/3i06 PDBsum]</span></td></tr>
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</table>
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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/i0/3i06_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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Trypanosoma cruzi and Trypanosoma brucei are parasites that cause Chagas' disease and African sleeping sickness, respectively. Both parasites rely on essential cysteine proteases for survival: cruzain for T. cruzi and TbCatB/rhodesain for T. brucei. A recent quantitative high-throughput screen of cruzain identified triazine nitriles, which are known inhibitors of other cysteine proteases, as reversible inhibitors of the enzyme. Structural modifications detailed herein, including core scaffold modification from triazine to purine, improved the in vitro potency against both cruzain and rhodesain by 350-fold, while also gaining activity against T. brucei parasites. Selected compounds were screened against a panel of human cysteine and serine proteases to determine selectivity, and a cocrystal was obtained of our most potent analogue bound to cruzain.
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==About this Structure==
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Identification and Optimization of Inhibitors of Trypanosomal Cysteine Proteases: Cruzain, Rhodesain, and TbCatB.,Mott BT, Ferreira RS, Simeonov A, Jadhav A, Ang KK, Leister W, Shen M, Silveira JT, Doyle PS, Arkin MR, McKerrow JH, Inglese J, Austin CP, Thomas CJ, Shoichet BK, Maloney DJ J Med Chem. 2009 Nov 12. PMID:19908842<ref>PMID:19908842</ref>
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[[3i06]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I06 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:019908842</ref><references group="xtra"/>
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</div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Cruzipain]]
[[Category: Cruzipain]]
[[Category: Trypanosoma cruzi]]
[[Category: Trypanosoma cruzi]]
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[[Category: Ferreira, R S.]]
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[[Category: Ferreira, R S]]
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[[Category: McKerrow, J H.]]
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[[Category: McKerrow, J H]]
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[[Category: Shoichet, B K.]]
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[[Category: Shoichet, B K]]
[[Category: Autocatalytic cleavage]]
[[Category: Autocatalytic cleavage]]
[[Category: Glycoprotein]]
[[Category: Glycoprotein]]

Revision as of 06:02, 18 December 2014

Crystal structure of cruzain covalently bound to a purine nitrile

3i06, resolution 1.10Å

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