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| | <StructureSection load='5mhf' size='340' side='right'caption='[[5mhf]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='5mhf' size='340' side='right'caption='[[5mhf]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mhf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MHF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MHF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mhf]] 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=5MHF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MHF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6A9:N-9-METHOXYNONYL-1-DEOXYNOJIRIMYCIN'>6A9</scene>, <scene name='pdbligand=7PG:2,5,8,11,14,17,20,23-OCTAOXAPENTACOSAN-25-OL'>7PG</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.1Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=SME:METHIONINE+SULFOXIDE'>SME</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6A9:N-9-METHOXYNONYL-1-DEOXYNOJIRIMYCIN'>6A9</scene>, <scene name='pdbligand=7PG:2,5,8,11,14,17,20,23-OCTAOXAPENTACOSAN-25-OL'>7PG</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SME:METHIONINE+SULFOXIDE'>SME</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mogs, Gcs1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5mhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mhf OCA], [https://pdbe.org/5mhf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mhf RCSB], [https://www.ebi.ac.uk/pdbsum/5mhf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mhf ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mannosyl-oligosaccharide_glucosidase Mannosyl-oligosaccharide glucosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.106 3.2.1.106] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mhf OCA], [http://pdbe.org/5mhf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mhf RCSB], [http://www.ebi.ac.uk/pdbsum/5mhf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mhf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MOGS_MOUSE MOGS_MOUSE]] Cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor. | + | [https://www.uniprot.org/uniprot/MOGS_MOUSE MOGS_MOUSE] Cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 26: |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Mannosyl-oligosaccharide glucosidase]]
| + | [[Category: Caputo AT]] |
| - | [[Category: Caputo, A T]] | + | [[Category: Hill JC]] |
| - | [[Category: Hill, J C]] | + | [[Category: Roversi P]] |
| - | [[Category: Roversi, P]] | + | [[Category: Zitzmann N]] |
| - | [[Category: Zitzmann, N]] | + | |
| - | [[Category: Gh63]]
| + | |
| - | [[Category: Glucosidase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Iminosugar]]
| + | |
| Structural highlights
5mhf is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.1Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
MOGS_MOUSE Cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor.
Publication Abstract from PubMed
Influenza and dengue viruses present a growing global threat to public health. Both viruses depend on the host endoplasmic reticulum (ER) glycoprotein folding pathway. In 2014, Sadat et al. reported two siblings with a rare genetic defect in ER alpha-glucosidase I (ER Glu I) who showed resistance to viral infections, identifying ER Glu I as a key antiviral target. Here, we show that a single dose of UV-4B (the hydrochloride salt form of N-(9'-methoxynonyl)-1-deoxynojirimycin; MON-DNJ) capable of inhibiting Glu I in vivo is sufficient to prevent death in mice infected with lethal viral doses, even when treatment is started as late as 48 h post infection. The first crystal structure of mammalian ER Glu I will constitute the basis for the development of potent and selective inhibitors. Targeting ER Glu I with UV-4B-derived compounds may alter treatment paradigms for acute viral disease through development of a single-dose therapeutic regime.
Targeting Endoplasmic Reticulum alpha-Glucosidase I with a Single-Dose Iminosugar Treatment Protects against Lethal Influenza and Dengue Virus Infections.,Warfield KL, Alonzi DS, Hill JC, Caputo AT, Roversi P, Kiappes JL, Sheets N, Duchars M, Dwek RA, Biggins J, Barnard D, Shresta S, Treston AM, Zitzmann N J Med Chem. 2020 Apr 15. doi: 10.1021/acs.jmedchem.0c00067. PMID:32227946[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Warfield KL, Alonzi DS, Hill JC, Caputo AT, Roversi P, Kiappes JL, Sheets N, Duchars M, Dwek RA, Biggins J, Barnard D, Shresta S, Treston AM, Zitzmann N. Targeting Endoplasmic Reticulum alpha-Glucosidase I with a Single-Dose Iminosugar Treatment Protects against Lethal Influenza and Dengue Virus Infections. J Med Chem. 2020 Apr 15. doi: 10.1021/acs.jmedchem.0c00067. PMID:32227946 doi:http://dx.doi.org/10.1021/acs.jmedchem.0c00067
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