5mhf

Murine endoplasmic reticulum alpha-glucosidase I with N-9'-methoxynonyl-1-deoxynojirimycin

spinqualitylabelsall models 5mhf, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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: 6A9, 7PG, BMA, MLY, NAG, SME, SO4 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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