scholarly journals ToP-DNJ, a Selective Inhibitor of Endoplasmic Reticulum α-Glucosidase II Exhibiting Antiflaviviral Activity

2017 ◽  
Vol 13 (1) ◽  
pp. 60-65 ◽  
Author(s):  
J. L. Kiappes ◽  
Michelle L. Hill ◽  
Dominic S. Alonzi ◽  
Joanna L. Miller ◽  
Ren Iwaki ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Selective Inhibitor ◽  
Glucosidase Ii

scholarly journals Structure of the Lectin Mannose 6-Phosphate Receptor Homology (MRH) Domain of Glucosidase II, an Enzyme That Regulates Glycoprotein Folding Quality Control in the Endoplasmic Reticulum

2013 ◽  
Vol 288 (23) ◽  
pp. 16460-16475 ◽  
Author(s):  
Linda J. Olson ◽  
Ramiro Orsi ◽  
Solana G. Alculumbre ◽  
Francis C. Peterson ◽  
Ivan D. Stigliano ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Three Dimensional ◽  
Binding Pocket ◽  
Dimensional Structure ◽  
Mannose Residue ◽  
Glucosidase Ii ◽  
Mannose 6 Phosphate ◽  
First Time ◽  
Conserved Residue

Here we report for the first time the three-dimensional structure of a mannose 6-phosphate receptor homology (MRH) domain present in a protein with enzymatic activity, glucosidase II (GII). GII is involved in glycoprotein folding in the endoplasmic reticulum. GII removes the two innermost glucose residues from the Glc3Man9GlcNAc2 transferred to nascent proteins and the glucose added by UDP-Glc:glycoprotein glucosyltransferase. GII is composed of a catalytic GIIα subunit and a regulatory GIIβ subunit. GIIβ participates in the endoplasmic reticulum localization of GIIα and mediates in vivo enhancement of N-glycan trimming by GII through its C-terminal MRH domain. We determined the structure of a functional GIIβ MRH domain by NMR spectroscopy. It adopts a β-barrel fold similar to that of other MRH domains, but its binding pocket is the most shallow known to date as it accommodates a single mannose residue. In addition, we identified a conserved residue outside the binding pocket (Trp-409) present in GIIβ but not in other MRHs that influences GII glucose trimming activity.

scholarly journals Substrate Specificity Analysis of Endoplasmic Reticulum Glucosidase II Using Synthetic High Mannose-type Glycans

2006 ◽  
Vol 281 (42) ◽  
pp. 31502-31508 ◽  
Author(s):  
Kiichiro Totani ◽  
Yoshito Ihara ◽  
Ichiro Matsuo ◽  
Yukishige Ito
Keyword(s):  
Endoplasmic Reticulum ◽  
Substrate Specificity ◽  
Glucosidase Ii ◽  
High Mannose

Virtual Screening Based on Pharmacophore to Discover Host ER Alpha-Glucosidase II Inhibitor for Dengue Therapy

2020 ◽  
Vol 840 ◽  
pp. 221-229
Author(s):  
Elsafira Ariavianti ◽  
Filia Stephanie ◽  
Usman Sumo Friend Tambunan
Keyword(s):  
Endoplasmic Reticulum ◽  
Natural Products ◽  
Molecular Docking ◽  
Drug Discovery ◽  
Virtual Screening ◽  
Host Protein ◽  
Binding Interaction ◽  
Ligand Interaction ◽  
Docking Simulations ◽  
Glucosidase Ii

Dengue is one of the crucial diseases in human-caused by dengue virus (DENV) infection. However, the development of DENV antiviral is often facing a problem because no effective drug to treat infection caused by all DENV serotypes. The inhibition of host protein involved in DENV life cycle can be a potential approach in dengue drug discovery, and also avoiding antiviral resistance. Endoplasmic Reticulum (ER) α-glucosidase II is one of the target host protein in DENV endoplasmic reticulum that plays an important role in the maturation process of DENV envelope glycoprotein. Natural products have been known as an essential source of a lead compound for drug discovery due to their therapeutic potency. In this research, pharmacophore-based virtual screening and molecular docking simulations were performed to find ligand that has potential to inhibit α-glucosidase II activity. About 67,609 natural products from InterBioScreen (IBS) database were used in the simulation as ligands with α-glucosidase II as the protein target. After subjected to Lipinski’s Rule of Five, druglikeness, nasty functions, and toxicity screening using DataWarrior software, 17,462 ligands were obtained. The pharmacophore features for molecular docking simulation was obtained from Protein-Ligand Interaction Fingerprint (PLIF) analysis using eight α-glucosidase II protein with different ligands. Based on virtual screening, rigid, and flexible docking simulations using Molecular Operating Environment (MOE) software, 32 ligands have lower Gibbs free binding energy (ΔGbinding) compared to the standards. Two best ligands, namely STOCK1N-85545 and STOCK1N-86400 which belong alkaloid derivatives, showed the exceptional ligand interaction and had the lowest ΔGbinding of-11.204 and-10.276 kcal/mol, respectively. The ligands were identified to have a binding interaction with amino acid Asp564 and Asp640 in α-glucosidase II catalytic site. STOCK1N-85545 and STOCK1N-86400 were also identified to have a good pharmacological properties after subjected to ADME-tox test using Toxtree, SwissADME, admetSAR, and pkCSM software.

scholarly journals Immunolocalization of the oligosaccharide trimming enzyme glucosidase II.

1986 ◽  
Vol 102 (6) ◽  
pp. 2137-2146 ◽  
Author(s):  
J M Lucocq ◽  
D Brada ◽  
J Roth
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Apparatus ◽  
Immunoelectron Microscopy ◽  
Transitional Region ◽  
Catabolic Pathway ◽  
Glucosidase Ii

We used immunoelectron microscopy to localize glucosidase II in pig hepatocytes. The enzyme trims the two inner alpha 1,3-linked glucoses from N-linked oligosaccharide precursor chains of glycoproteins. Immunoreactive enzyme was concentrated in rough (RER) and smooth (SER) endoplasmic reticulum but not detectable in Golgi apparatus cisternae. Transitional elements of RER and smooth membraned structures close to Golgi apparatus cisternae contained labeling for glucosidase II. Specific labeling was also found in autophagosomes. These results indicate strongly that glucosidase II acts on glycoproteins before their transport to, and processing in Golgi apparatus cisternae, and suggest that an important transitional region for glucosidase II exists between RER and Golgi apparatus cisternae. Degradation in autophagolysosomes could form a normal catabolic pathway for glucosidase II.

Isolation and functional characterization of Sporothrix schenckii ROT2, the encoding gene for the endoplasmic reticulum glucosidase II

2012 ◽  
Vol 116 (8) ◽  
pp. 910-918 ◽  
Author(s):  
Claudia I. Robledo-Ortiz ◽  
Arturo Flores-Carreón ◽  
Arturo Hernández-Cervantes ◽  
Aurelio Álvarez-Vargas ◽  
Keunsook K. Lee ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Functional Characterization ◽  
Sporothrix Schenckii ◽  
Glucosidase Ii ◽  
Encoding Gene

scholarly journals Endoplasmic Reticulum Glucosidase II Is Required for Pathogenicity of Ustilago maydis

2005 ◽  
Vol 17 (12) ◽  
pp. 3532-3543 ◽  
Author(s):  
Jan Schirawski ◽  
Heidi U. Böhnert ◽  
Gero Steinberg ◽  
Karen Snetselaar ◽  
Lubica Adamikowa ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Ustilago Maydis ◽  
Glucosidase Ii

scholarly journals Uncoupling of sustained MAMP receptor signaling from early outputs in an Arabidopsis endoplasmic reticulum glucosidase II allele

2009 ◽  
Vol 106 (52) ◽  
pp. 22522-22527 ◽  
Author(s):  
Xunli Lu ◽  
Nico Tintor ◽  
Tobias Mentzel ◽  
Erich Kombrink ◽  
Thomas Boller ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Receptor Signaling ◽  
Glucosidase Ii

scholarly journals Conformational Requirements for Glycoprotein Reglucosylation in the Endoplasmic Reticulum

2000 ◽  
Vol 148 (6) ◽  
pp. 1123-1130 ◽  
Author(s):  
E. Sergio Trombetta ◽  
Ari Helenius
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Protein Conformations ◽  
Glucosidase Ii ◽  
Discrete Populations

Newly synthesized glycoproteins interact during folding and quality control in the ER with calnexin and calreticulin, two lectins specific for monoglucosylated oligosaccharides. Binding and release are regulated by two enzymes, glucosidase II and UDP-Glc:glycoprotein:glycosyltransferase (GT), which cyclically remove and reattach the essential glucose residues on the N-linked oligosaccharides. GT acts as a folding sensor in the cycle, selectively reglucosylating incompletely folded glycoproteins and promoting binding of its substrates to the lectins. To investigate how nonnative protein conformations are recognized and directed to this unique chaperone system, we analyzed the interaction of GT with a series of model substrates with well defined conformations derived from RNaseB. We found that conformations with slight perturbations were not reglucosylated by GT. In contrast, a partially structured nonnative form was efficiently recognized by the enzyme. When this form was converted back to a nativelike state, concomitant loss of recognition by GT occurred, reproducing the reglucosylation conditions observed in vivo with isolated components. Moreover, fully unfolded conformers were poorly recognized. The results indicated that GT is able to distinguish between different nonnative conformations with a distinct preference for partially structured conformers. The findings suggest that discrete populations of nonnative conformations are selectively reglucosylated to participate in the calnexin/calreticulin chaperone pathway.

scholarly journals Screening Identifies Thimerosal as a Selective Inhibitor of Endoplasmic Reticulum Aminopeptidase 1

2016 ◽  
Vol 7 (7) ◽  
pp. 681-685 ◽  
Author(s):  
Athanasios Stamogiannos ◽  
Athanasios Papakyriakou ◽  
Francois-Xavier Mauvais ◽  
Peter van Endert ◽  
Efstratios Stratikos
Keyword(s):  
Endoplasmic Reticulum ◽  
Selective Inhibitor ◽  
Endoplasmic Reticulum Aminopeptidase 1
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