View source for 6mwy


==The Prp8 intein of Cryptococcus gattii==
<StructureSection load='6mwy' size='340' side='right'caption='[[6mwy]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mwy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_gattii_VGII_R265 Cryptococcus gattii VGII R265]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MWY 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]] 2.594&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=6mwy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mwy OCA], [https://pdbe.org/6mwy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mwy RCSB], [https://www.ebi.ac.uk/pdbsum/6mwy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mwy ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Prp8 intein is one of the most widespread eukaryotic inteins, present in important pathogenic fungi, including Cryptococcus and Aspergillus species. Because the processed Prp8 carries out essential and non-redundant cellular functions, a Prp8 intein inhibitor is a mechanistically novel antifungal agent. In this report, we demonstrated that cisplatin, an FDA-approved cancer drug, significantly arrested growth of Prp8 intein-containing fungi C. neoformans and C. gattii, but only poorly inhibited growth of intein-free Candida species. These results suggest that cisplatin arrests fungal growth through specific inhibition of the Prp8 intein. Cisplatin was also found to significantly inhibit growth of C. neoformans in a mouse model. Our results further showed that cisplatin inhibited Prp8 intein splicing in vitro in a dose-dependent manner by direct binding to the Prp8 intein. Crystal structures of the apo- and cisplatin-bound Prp8 inteins revealed that two degenerate cisplatin molecules bind at the intein active site. Mutation of the splicing-site residues led to loss of cisplatin binding, as well as impairment of intein splicing. Finally, we found that overexpression of the Prp8 intein in cryptococcal species conferred cisplatin resistance. Overall, these results indicate that the Prp8 intein is a novel antifungal target worth further investigation.

Cisplatin protects mice from challenge of Cryptococcus neoformans by targeting the Prp8 intein.,Li Z, Fu B, Green CM, Liu B, Zhang J, Lang Y, Chaturvedi S, Belfort M, Liao G, Li H Emerg Microbes Infect. 2019;8(1):895-908. doi: 10.1080/22221751.2019.1625727. PMID:31223062<ref>PMID:31223062</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6mwy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cryptococcus gattii VGII R265]]
[[Category: Large Structures]]
[[Category: Belfort M]]
[[Category: Callahan BP]]
[[Category: Chaturvedi S]]
[[Category: Fu B]]
[[Category: Green CM]]
[[Category: Lang Y]]
[[Category: Li H]]
[[Category: Li X]]
[[Category: Li Z]]
[[Category: Liao G]]
[[Category: Oven TS]]
[[Category: Zhang J]]