View source for 3kku


==Cruzain in complex with a non-covalent ligand==
<StructureSection load='3kku' size='340' side='right'caption='[[3kku]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3kku]] is a 1 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=3KKU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.28&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kku OCA], [https://pdbe.org/3kku PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kku RCSB], [https://www.ebi.ac.uk/pdbsum/3kku PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kku ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CYSP_TRYCR CYSP_TRYCR] Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group.  The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.
== 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/initialview03.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/main_output.php?pdb_ID=3kku 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3kku" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cruzain|Cruzain]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma cruzi]]
[[Category: Eidam O]]
[[Category: Ferreira RS]]
[[Category: Shoichet BK]]