7jty
From Proteopedia
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| - | ==== | + | ==Co-crystal structure of alpha glucosidase with compound 1== |
| - | <StructureSection load='7jty' size='340' side='right'caption='[[7jty]]' scene=''> | + | <StructureSection load='7jty' size='340' side='right'caption='[[7jty]], [[Resolution|resolution]] 2.21Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7jty]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JTY FirstGlance]. <br> |
| - | </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=7jty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jty OCA], [https://pdbe.org/7jty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jty RCSB], [https://www.ebi.ac.uk/pdbsum/7jty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jty ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.21Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VND:(1S,2S,3R,4S,5S)-5-(butylamino)-1-(hydroxymethyl)cyclohexane-1,2,3,4-tetrol'>VND</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=7jty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jty OCA], [https://pdbe.org/7jty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jty RCSB], [https://www.ebi.ac.uk/pdbsum/7jty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jty ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GANAB_MOUSE GANAB_MOUSE] Cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Most enveloped viruses rely on the host cell endoplasmic reticulum (ER) quality control (QC) machinery for proper folding of glycoproteins. The key ER alpha-glucosidases (alpha-Glu) I and II of the ERQC machinery are attractive targets for developing broad-spectrum antivirals. Iminosugars based on deoxynojirimycin have been extensively studied as ER alpha-glucosidase inhibitors; however, other glycomimetic compounds are less established. Accordingly, we synthesized a series of N-substituted derivatives of valiolamine, the iminosugar scaffold of type 2 diabetes drug voglibose. To understand the basis for up to 100,000-fold improved inhibitory potency, we determined high-resolution crystal structures of mouse ER alpha-GluII in complex with valiolamine and 10 derivatives. The structures revealed extensive interactions with all four alpha-GluII subsites. We further showed that N-substituted valiolamines were active against dengue virus and SARS-CoV-2 in vitro. This study introduces valiolamine-based inhibitors of the ERQC machinery as candidates for developing potential broad-spectrum therapeutics against the existing and emerging viruses. | ||
| + | |||
| + | N-Substituted Valiolamine Derivatives as Potent Inhibitors of Endoplasmic Reticulum alpha-Glucosidases I and II with Antiviral Activity.,Karade SS, Hill ML, Kiappes JL, Manne R, Aakula B, Zitzmann N, Warfield KL, Treston AM, Mariuzza RA J Med Chem. 2021 Dec 23;64(24):18010-18024. doi: 10.1021/acs.jmedchem.1c01377. , Epub 2021 Dec 6. PMID:34870992<ref>PMID:34870992</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7jty" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Mus musculus]] |
| + | [[Category: Karade SS]] | ||
| + | [[Category: Mariuzza RA]] | ||
Current revision
Co-crystal structure of alpha glucosidase with compound 1
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