View source for 4xui


==Crystal structure analysis of cruzain bound to the no-covalent analog of WRR-483 (WRR-669)==
<StructureSection load='4xui' size='340' side='right'caption='[[4xui]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xui]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4pi4 4pi4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XUI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XUI 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]] 2.508&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2VC:N-[(2S)-5-(CARBAMIMIDAMIDOOXY)-1-OXO-1-{[(1E,3S)-5-PHENYL-1-(PYRIMIDIN-2-YLSULFONYL)PENT-1-EN-3-YL]AMINO}PENTAN-2-YL]-4-METHYLPIPERAZINE-1-CARBOXAMIDE'>2VC</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4xui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xui OCA], [https://pdbe.org/4xui PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xui RCSB], [https://www.ebi.ac.uk/pdbsum/4xui PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xui 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.
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== Publication Abstract from PubMed ==
A series of oxyguanidine analogues of the cysteine protease inhibitor WRR-483 were synthesized and evaluated against cruzain, the major cysteine protease of the protozoan parasite Trypanosoma cruzi. Kinetic analyses of these analogues indicated that they have comparable potency to previously prepared vinyl sulfone cruzain inhibitors. Co-crystal structures of the oxyguanidine analogues WRR-666 (4) and WRR-669 (7) bound to cruzain demonstrated different binding interactions with the cysteine protease, depending on the aryl moiety of the P1' inhibitor subunit. Specifically, these data demonstrate that WRR-669 is bound noncovalently in the crystal structure. This represents a rare example of noncovalent inhibition of a cysteine protease by a vinyl sulfone inhibitor.

Synthesis and Evaluation of Oxyguanidine Analogues of the Cysteine Protease Inhibitor WRR-483 against Cruzain.,Jones BD, Tochowicz A, Tang Y, Cameron MD, McCall LI, Hirata K, Siqueira-Neto JL, Reed SL, McKerrow JH, Roush WR ACS Med Chem Lett. 2015 Dec 15;7(1):77-82. doi: 10.1021/acsmedchemlett.5b00336., eCollection 2016 Jan 14. PMID:26819670<ref>PMID:26819670</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 4xui" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cruzain|Cruzain]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma cruzi]]
[[Category: McKerrow JH]]
[[Category: Tochowicz A]]