View source for 1ewp


==CRUZAIN BOUND TO MOR-LEU-HPQ==
<StructureSection load='1ewp' size='340' side='right'caption='[[1ewp]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ewp]] 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=1EWP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EWP 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0I5:N-[(3S)-1-FLUORO-2-OXO-5-PHENYLPENTAN-3-YL]-N~2~-(MORPHOLIN-4-YLCARBONYL)-L-LEUCINAMIDE'>0I5</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=1ewp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ewp OCA], [https://pdbe.org/1ewp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ewp RCSB], [https://www.ebi.ac.uk/pdbsum/1ewp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ewp 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/ew/1ewp_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=1ewp ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Trypanosoma cruzi, a protozoan parasite, is the etiologic agent of American trypanosomiasis or Chagas' disease. Chagas' disease afflicts more than 24 million individuals in South and Central America producing a debilitating life-long disease. It is the leading cause of heart failure in many Latin American countries. Currently, there is no satisfactory treatment for this parasitic infection. Cruzain (also known as cruzipain, gp 57/51), the major cysteine protease present in T. cruzi, is critical for the development and survival of the parasite within the host cells, making this enzyme a target for potential trypanocidal drugs. Here we report the X-ray crystal structure of cruzain complexed with the potent inhibitor Z-Phe-Ala-fluoromethyl ketone. The structure was determined at 2.35 A (Rcryst = 0.15) by molecular replacement using a modified papain as the search model. The refined structure is compared to papain. Features which distinguish cruzain from papain are discussed since they may aid in the design of specificity inhibitors. Fluorescence microscopy shows that a biotinylated form of the bound inhibitor does not effectively reach host proteases in their lysosomal compartment, but is selectively taken up by the parasite. The inhibitor greatly reduces parasitemia in a cell culture system, without adverse effects to mammalian cells. This biological selectivity can be exploited, in conjunction with unique active site features revealed by the crystal structure, to develop chemotherapy for Chagas' disease.

The crystal structure of cruzain: a therapeutic target for Chagas' disease.,McGrath ME, Eakin AE, Engel JC, McKerrow JH, Craik CS, Fletterick RJ J Mol Biol. 1995 Mar 24;247(2):251-9. PMID:007707373<ref>PMID:007707373</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1ewp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cruzain|Cruzain]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma cruzi]]
[[Category: Gillmor SA]]