View source for 7rd2


==Co-crystal structure of Chaetomium glucosidase with compound 2==
<StructureSection load='7rd2' size='340' side='right'caption='[[7rd2]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7rd2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum_var._thermophilum_DSM_1495 Chaetomium thermophilum var. thermophilum DSM 1495]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RD2 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]] 2.61&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5X7:(2~{R},3~{R},4~{R},5~{S})-1-[[4-[[[4-[(2~{S},6~{R})-2,6-dimethylmorpholin-4-yl]-2-nitro-phenyl]amino]methyl]phenyl]methyl]-2-(hydroxymethyl)piperidine-3,4,5-triol'>5X7</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7rd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rd2 OCA], [https://pdbe.org/7rd2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rd2 RCSB], [https://www.ebi.ac.uk/pdbsum/7rd2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rd2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G0SFD1_CHATD G0SFD1_CHATD] 
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== Publication Abstract from PubMed ==
Enveloped viruses depend on the host endoplasmic reticulum (ER) quality control (QC) machinery for proper glycoprotein folding. The endoplasmic reticulum quality control (ERQC) enzyme alpha-glucosidase I (alpha-GluI) is an attractive target for developing broad-spectrum antivirals. We synthesized 28 inhibitors designed to interact with all four subsites of the alpha-GluI active site. These inhibitors are derivatives of the iminosugars 1-deoxynojirimycin (1-DNJ) and valiolamine. Crystal structures of ER alpha-GluI bound to 25 1-DNJ and three valiolamine derivatives revealed the basis for inhibitory potency. We established the structure-activity relationship (SAR) and used the Site Identification by Ligand Competitive Saturation (SILCS) method to develop a model for predicting alpha-GluI inhibition. We screened the compounds against SARS-CoV-2 in vitro to identify those with greater antiviral activity than the benchmark alpha-glucosidase inhibitor UV-4. These host-targeting compounds are candidates for investigation in animal models of SARS-CoV-2 and for testing against other viruses that rely on ERQC for correct glycoprotein folding.

Structure-Based Design of Potent Iminosugar Inhibitors of Endoplasmic Reticulum alpha-Glucosidase I with Anti-SARS-CoV-2 Activity.,Karade SS, Franco EJ, Rojas AC, Hanrahan KC, Kolesnikov A, Yu W, MacKerell AD Jr, Hill DC, Weber DJ, Brown AN, Treston AM, Mariuzza RA J Med Chem. 2023 Feb 23;66(4):2744-2760. doi: 10.1021/acs.jmedchem.2c01750. Epub , 2023 Feb 10. PMID:36762932<ref>PMID:36762932</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7rd2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Chaetomium thermophilum var. thermophilum DSM 1495]]
[[Category: Large Structures]]
[[Category: Karade SS]]
[[Category: Mariuzza RA]]