Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.20 (alpha-glucosidase)
 4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six groups, designated a-f, of noncompeting murine monoclonal antibodies to the envelope glycoprotein E2 of Semliki Forest virus (SFV) have been used to analyze antigenic changes caused by differences in the carbohydrate chain composition of the envelope glycoprotein E2 in the virion. Deletion of terminal sialic acids as observed in virus progeny from mosquito cells did not affect antigenic properties. Inhibition of the trimming pathway in infected chicken cells by the mannosidase I inhibitor dMM led to infectious virus particles containing mannose-rich oligosaccharides of the composition Man9(GlcNAc)2 in the envelope glycoproteins. This alteration had no effect on antigenicity. If inhibition was, however, performed with MdN which acts on alpha-glucosidase giving rise to virions with glycoproteins containing three additional glucose residues in the carbohydrate chains [Glc3Man7,8,9(GlcNAc)2], significant antigenic changes were observed. The six epitopes were differently affected by the underlying structural change and the pattern of exposition of epitopes was not identical with that observed after cleavage of intramolecular disulfide bonds. Concomitantly, the cleavage rate of gp62, the intracellular precursor molecule of the glycoproteins E2 and E3 of the virus particle, was reduced causing a reduction of virus yield. It is concluded that the existence of untrimmed carbohydrate chains is sufficient to allow SFV maturation. The trimming reactions improve this process in a matter suggesting that the carbohydrate chains influence intracellular traffic (addressing) of the respective glycoprotein.
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PMID:The significance of carbohydrate trimming for the antigenicity of the Semliki Forest virus glycoprotein E2. 169 45

Glycoprotein processing inhibitors prevent the normal processing of N-linked glycoproteins by inhibiting specific glycosidases involved in these reactions. Thus, a number of compounds are now known that inhibit alpha-glucosidase I and alpha-glucosidase II and therefore prevent the removal of glucoses from the high-mannose chains. Some of these compounds are more potent inhibitors of one or the other of these glucosidases. There are also a number of inhibitors that affect one of the processing alpha-mannosidases (i.e. mannosidase I or mannosidase II). These compounds; especially the glucosidase inhibitors, have been valuable tools to help us understand the role of carbohydrate in viral envelope glycoprotein function. Such processing inhibitors have also been used with various tumorigenic cell lines to determine the function of N-linked glycoproteins in cancer.
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PMID:Glycosidase inhibitors as antiviral and/or antitumor agents. 181 22

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) is a plant alkaloid that modifies glycosylation by inhibiting alpha-glucosidase I. Castanospermine is shown to inhibit syncytium formation induced by the envelope glycoprotein of the human immunodeficiency virus and to inhibit viral replication. The decrease in syncytium formation in the presence of castanospermine can be attributed to inhibition of processing of the envelope precursor protein gp160, with resultant decreased cell surface expression of the mature envelope glycoprotein gp120. In addition, castanospermine may cause defects in steps involved in membrane fusion after binding of CD4 antigen. The antiviral effects of castanospermine may be due to modifications of the envelope glycoprotein that affect the ability of the virus to enter cells after attachment to the CD4 cell receptor.
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PMID:Inhibition of human immunodeficiency virus syncytium formation and virus replication by castanospermine. 282 77

The alpha-glucosidase inhibitor N-butyldeoxynojirimycin (NB-DNJ) is an inhibitor of human immunodeficiency virus (HIV) replication and HIV-induced syncytium formation in vitro. Although an NB-DNJ-mediated change in viral envelope N-glycan composition inhibits HIV entry at the level of post-CD4 binding, the exact mechanism of inhibition remains to be established. In this study we have examined the effects of NB-DNJ on virion envelope composition and CD4-induced gp120 shedding and gp41 exposure. Virion composition analysis revealed an NB-DNJ-mediated reduction of 15% in overall virion envelope glycoprotein content and a reduction of 26% in the proteolytic maturation of virion gp160. Taken together, these two effects resulted in a reduction of approximately 40% in virion gp120 content. CD4-induced shedding of gp120 from the surfaces of envelope-transfected Cos cells was undetectable when gp120 was expressed in the presence of NB-DNJ. Similarly, the shedding of virion-associated gp120 was reduced 7.4-fold. CD4-induced exposure of cryptic gp41 epitopes on the surfaces of HIV-expressing ACH-2 cells was also greatly impaired, and the exposure of virion-associated gp41 epitopes was reduced 4.0-fold. Finally, CD4-induced increases in the binding of antibodies to the V3 loop of ACH-2-cell-expressed envelope glycoproteins were reduced 25-fold when the glycoproteins were expressed in the presence of NB-DNJ. These results suggest that the NB-DNJ-mediated retention of glycosylated N-glycans inhibits HIV entry by a combined effect of a reduction in virion gp120 content and a qualitative defect within the remaining gp120, preventing it from undergoing conformational changes after CD4 binding.
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PMID:N-butyldeoxynojirimycin-mediated inhibition of human immunodeficiency virus entry correlates with impaired gp120 shedding and gp41 exposure. 879 62

We report that endoplasmic reticulum alpha-glucosidase inhibitors have antiviral effects on dengue (DEN) virus. We found that glucosidase inhibition strongly affects productive folding pathways of the envelope glycoproteins prM (the intracellular glycosylated precursor of M [membrane protein]) and E (envelope protein): the proper folding of prM bearing unprocessed N-linked oligosaccharide is inefficient, and this causes delayed formation of prME heterodimer. The complexes formed between incompletely folded prM and E appear to be unstable, leading to a nonproductive pathway. Inhibition of alpha-glucosidase-mediated N-linked oligosaccharide trimming may thus prevent the assembly of DEN virus by affecting the early stages of envelope glycoprotein processing.
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PMID:Alpha-glucosidase inhibitors reduce dengue virus production by affecting the initial steps of virion morphogenesis in the endoplasmic reticulum. 1059 Jan 51

Mannose-binding lectin (MBL), a C-type lectin component of the human innate immune system, binds to the gp120 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1). The objective of this study was to assess the effects of inhibitors of endoplasmic reticulum glucosidases and Golgi mannosidase as well as neuraminidase (NA) on the interaction between HIV and MBL. Production of HIV in the presence of the mannosidase I inhibitor deoxymannojirimycin (dMM) significantly enhanced binding of HIV to MBL and increased MBL neutralization of an M-tropic HIV primary isolate. In contrast, culturing HIV in the presence of alpha-glucosidase I and II inhibitors castanospermine and deoxynojirimycin only slightly affected virus binding and neutralization by MBL. Removal of sialic acid from HIV by NA also significantly enhanced virus binding and neutralization by MBL. Treatment of virus grown in the presence of dMM with endoglycosidase F1 substantially reduced binding to MBL, indicating that dMM increased MBL binding by increasing high-mannose carbohydrates on the virus. In contrast, endoglycosidase F1 did not decrease the MBL interaction with NA-treated virus, suggesting that NA exposed novel MBL binding sites. Treatment with dMM increased the immunocapture of HIV by monoclonal antibodies 2F5 and 2G12, indicating that altering the glycosylation of viral glycoproteins increases the accessibility or reactivity of some epitopes. This study shows that specific alterations of the N-linked carbohydrates on HIV gp120/gp41 can enhance MBL-mediated neutralization of virus by strengthening the interaction of HIV-1 with MBL.
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PMID:Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin. 1256 May 67

Endoplasmic reticulum (ER) alpha-glucosidase inhibitors block the trimming of N-linked glycosylation and thus prevent the production of several viruses. The present study investigates the antiviral effects of the alpha-glucosidase and alpha-mannosidase inhibitors (castanospermine, 1-deoxynojirimycin, bromoconduritol, deoxymannojirimycin and swainsonine) on human parainfluenza virus type 3 (HPIV3). The alpha-glucosidase inhibitors (castanospermine, 1-deoxynojirimycin) in recombinant expression systems reduced the surface and intracellular expression of both HPIV3 F and HN proteins. On the other hand, alpha-mannosidase inhibitors prevented processing of the oligosaccharides on HPIV3 glycoproteins into the complex form. Consequently, alpha-glycosidase inhibitors (castanospermine and 1-deoxynojirimycin) significantly inhibited viral fusion activity. We demonstrated that the alpha-glucosidase inhibitors (castanospermine and 1-deoxynojirimycin) reduced the infectivity of newly released viral particles. We postulate that alpha-glucosidase inhibitors can prevent the first steps of HPIV3 envelope glycoprotein processing and that the inhibition of glucose trimming has antiviral effects.
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PMID:Antiviral effects of glycosylation and glucose trimming inhibitors on human parainfluenza virus type 3. 1673 76