View source for 6q55


==Crystal structure of Cryptosporidium hominis CPSF3 in complex with Compound 61==
<StructureSection load='6q55' size='340' side='right'caption='[[6q55]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6q55]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptosporidium_hominis_TU502 Cryptosporidium hominis TU502]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q55 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HJB:3-[7,7-bis(oxidanyl)-8-oxa-7-boranuidabicyclo[4.3.0]nona-1(6),2,4-trien-5-yl]propanoic+acid'>HJB</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6q55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q55 OCA], [https://pdbe.org/6q55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q55 RCSB], [https://www.ebi.ac.uk/pdbsum/6q55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q55 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0S4TJL4_CRYHO A0A0S4TJL4_CRYHO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cryptosporidium is an intestinal pathogen that causes severe but self-limiting diarrhea in healthy humans, yet it can turn into a life-threatening, unrelenting infection in immunocompromised patients and young children. Severe diarrhea is recognized as the leading cause of mortality for children below 5 years of age in developing countries. The only approved treatment against cryptosporidiosis, nitazoxanide, has limited efficacy in the most vulnerable patient populations, including malnourished children, and is ineffective in immunocompromised individuals. Here, we investigate inhibition of the parasitic cleavage and polyadenylation specificity factor 3 (CPSF3) as a strategy to control Cryptosporidium infection. We show that the oxaborole AN3661 selectively blocked Cryptosporidium growth in human HCT-8 cells, and oral treatment with AN3661 reduced intestinal parasite burden in both immunocompromised and neonatal mouse models of infection with greater efficacy than nitazoxanide. Furthermore, we present crystal structures of recombinantly produced Cryptosporidium CPSF3, revealing a mechanism of action whereby the mRNA processing activity of this enzyme is efficiently blocked by the binding of the oxaborole group at the metal-dependent catalytic center. Our data provide insights that may help accelerate the development of next-generation anti-Cryptosporidium therapeutics.

Metal-captured inhibition of pre-mRNA processing activity by CPSF3 controls Cryptosporidium infection.,Swale C, Bougdour A, Gnahoui-David A, Tottey J, Georgeault S, Laurent F, Palencia A, Hakimi MA Sci Transl Med. 2019 Nov 6;11(517). pii: 11/517/eaax7161. doi:, 10.1126/scitranslmed.aax7161. PMID:31694928<ref>PMID:31694928</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6q55" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Cryptosporidium hominis TU502]]
[[Category: Large Structures]]
[[Category: Palencia A]]
[[Category: Swale C]]