8ekn: Difference between revisions

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-'''Unreleased structure'''
-The entry 8ekn is ON HOLD  until Paper Publication
+==Co-crystal structure of Chaetomium glucosidase with compound 15==
+<StructureSection load='8ekn' size='340' side='right'caption='[[8ekn]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8ekn]] 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=8EKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EKN FirstGlance]. <br>
+</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WLQ:(2R,3R,4R,5S)-2-(hydroxymethyl)-1-{[4-({[(5P)-3-methyl-5-(pyridazin-3-yl)phenyl]amino}methyl)phenyl]methyl}piperidine-3,4,5-triol'>WLQ</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=8ekn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ekn OCA], [https://pdbe.org/8ekn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ekn RCSB], [https://www.ebi.ac.uk/pdbsum/8ekn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ekn ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/G0SFD1_CHATD G0SFD1_CHATD]
+<div style="background-color:#fffaf0;">
+== 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.
-Authors:
+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 10. doi: 10.1021/acs.jmedchem.2c01750. PMID:36762932<ref>PMID:36762932</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8ekn" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Chaetomium thermophilum var. thermophilum DSM 1495]]
+[[Category: Large Structures]]
+[[Category: Karade SS]]
+[[Category: Mariuzza RA]]