3kku: Difference between revisions
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==Cruzain in complex with a non-covalent ligand== | |||
=== | <StructureSection load='3kku' size='340' side='right' caption='[[3kku]], [[Resolution|resolution]] 1.28Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3kku]] 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=3KKU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KKU FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B95:N-[2-(1H-BENZIMIDAZOL-2-YL)ETHYL]-2-(2-BROMOPHENOXY)ACETAMIDE'>B95</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=Z22:S-METHYL+METHANESULFONOTHIOATE'>Z22</scene></td></tr> | |||
<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> | |||
<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=3kku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kku OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kku RCSB], [http://www.ebi.ac.uk/pdbsum/3kku PDBsum]</span></td></tr> | |||
</table> | |||
== 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/kk/3kku_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Virtual and high-throughput screens (HTS) should have complementary strengths and weaknesses, but studies that prospectively and comprehensively compare them are rare. We undertook a parallel docking and HTS screen of 197861 compounds against cruzain, a thiol protease target for Chagas disease, looking for reversible, competitive inhibitors. On workup, 99% of the hits were eliminated as false positives, yielding 146 well-behaved, competitive ligands. These fell into five chemotypes: two were prioritized by scoring among the top 0.1% of the docking-ranked library, two were prioritized by behavior in the HTS and by clustering, and one chemotype was prioritized by both approaches. Determination of an inhibitor/cruzain crystal structure and comparison of the high-scoring docking hits to experiment illuminated the origins of docking false-negatives and false-positives. Prioritizing molecules that are both predicted by docking and are HTS-active yields well-behaved molecules, relatively unobscured by the false-positives to which both techniques are individually prone. | |||
Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors.,Ferreira RS, Simeonov A, Jadhav A, Eidam O, Mott BT, Keiser MJ, McKerrow JH, Maloney DJ, Irwin JJ, Shoichet BK J Med Chem. 2010 Jul 8;53(13):4891-905. PMID:20540517<ref>PMID:20540517</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cruzipain]] | [[Category: Cruzipain]] | ||
[[Category: Trypanosoma cruzi]] | [[Category: Trypanosoma cruzi]] | ||
[[Category: Eidam, O | [[Category: Eidam, O]] | ||
[[Category: Ferreira, R S | [[Category: Ferreira, R S]] | ||
[[Category: Shoichet, B K | [[Category: Shoichet, B K]] | ||
[[Category: Autocatalytic cleavage]] | [[Category: Autocatalytic cleavage]] | ||
[[Category: Glycoprotein]] | [[Category: Glycoprotein]] | ||
Revision as of 20:02, 18 December 2014
Cruzain in complex with a non-covalent ligandCruzain in complex with a non-covalent ligand
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedVirtual and high-throughput screens (HTS) should have complementary strengths and weaknesses, but studies that prospectively and comprehensively compare them are rare. We undertook a parallel docking and HTS screen of 197861 compounds against cruzain, a thiol protease target for Chagas disease, looking for reversible, competitive inhibitors. On workup, 99% of the hits were eliminated as false positives, yielding 146 well-behaved, competitive ligands. These fell into five chemotypes: two were prioritized by scoring among the top 0.1% of the docking-ranked library, two were prioritized by behavior in the HTS and by clustering, and one chemotype was prioritized by both approaches. Determination of an inhibitor/cruzain crystal structure and comparison of the high-scoring docking hits to experiment illuminated the origins of docking false-negatives and false-positives. Prioritizing molecules that are both predicted by docking and are HTS-active yields well-behaved molecules, relatively unobscured by the false-positives to which both techniques are individually prone. Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors.,Ferreira RS, Simeonov A, Jadhav A, Eidam O, Mott BT, Keiser MJ, McKerrow JH, Maloney DJ, Irwin JJ, Shoichet BK J Med Chem. 2010 Jul 8;53(13):4891-905. PMID:20540517[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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