View source for 7lpo


==Crystal structure of Cryptococcus neoformans sterylglucosidase 1 with tris==
<StructureSection load='7lpo' size='340' side='right'caption='[[7lpo]], [[Resolution|resolution]] 2.13&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lpo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptococcus_neoformans_var._grubii_H99 Cryptococcus neoformans var. grubii H99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LPO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LPO 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]] 2.13&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=7lpo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lpo OCA], [https://pdbe.org/7lpo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lpo RCSB], [https://www.ebi.ac.uk/pdbsum/7lpo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lpo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/J9W473_CRYNH J9W473_CRYNH] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pathogenic fungi exhibit a heavy burden on medical care and new therapies are needed. Here, we develop the fungal specific enzyme sterylglucosidase 1 (Sgl1) as a therapeutic target. Sgl1 converts the immunomodulatory glycolipid ergosterol 3beta-D-glucoside to ergosterol and glucose. Previously, we found that genetic deletion of Sgl1 in the pathogenic fungus Cryptococcus neoformans (Cn) results in ergosterol 3beta-D-glucoside accumulation, renders Cn non-pathogenic, and immunizes mice against secondary infections by wild-type Cn, even in condition of CD4+ T cell deficiency. Here, we disclose two distinct chemical classes that inhibit Sgl1 function in vitro and in Cn cells. Pharmacological inhibition of Sgl1 phenocopies a growth defect of the Cn Deltasgl1 mutant and prevents dissemination of wild-type Cn to the brain in a mouse model of infection. Crystal structures of Sgl1 alone and with inhibitors explain Sgl1's substrate specificity and enable the rational design of antifungal agents targeting Sgl1.

Structure and inhibition of Cryptococcus neoformans sterylglucosidase to develop antifungal agents.,Pereira de Sa N, Taouil A, Kim J, Clement T, Hoffmann RM, Burke JE, Rizzo RC, Ojima I, Del Poeta M, Airola MV Nat Commun. 2021 Oct 7;12(1):5885. doi: 10.1038/s41467-021-26163-5. PMID:34620873<ref>PMID:34620873</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lpo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cryptococcus neoformans var. grubii H99]]
[[Category: Large Structures]]
[[Category: Airola MV]]
[[Category: Del Poeta M]]
[[Category: Pereira de Sa N]]