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)

Phytohemagglutinin, the glycoprotein lectin of the common bean, Phaseolus vulgaris, has both high-mannose (Man(8-9)GlcNAc(2)) and modified oligosaccharide side chains. The modified side chains have glucosamine, mannose, fucose, and xylose in the molar ratios 2:3.8:0.6:0.5, and are resistant to hydrolysis by endoglycosidase H. Synthesis and processing of side chains in the presence of 1-deoxynojirimycin, an inhibitor of alpha-glucosidase, results in the formation of chains which are all alike. They are sensitive to endoglycosidase H, do not contain fucose, and are largely resistant to alpha-mannosidase. This indicates that they are probably high-mannose chains blocked by terminal glucose residues. Synthesis and processing of side chains in the presence of swainsonine, an inhibitor of alpha-mannosidase II, results in the formation of normal high-mannose chains, and of modified chains which contain fucose residues, are resistant to endoglycosidase H, and can be distinguished from normal modified chains only by the presence of extra mannose residues.Processing of the phytohemagglutinin modified chains of PHA under normal conditions involves the attachment of peripheral N-acetylglucosamine residues in the Golgi complex and their subsequent removal in the protein bodies. The attachment of the N-acetylglucosamine residues is largely inhibited by deoxynojirimycin but still occurs in the presence of swainsonine. The results presented in this work show that processing of the asparagine-linked oligosaccharides is under the control of several glycosidases and glycosyltransferases and involves the formation of intermediate products.
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PMID:Abnormal processing of the modified oligosaccharide side chains of phytohemagglutinin in the presence of swainsonine and deoxynojirimycin. 1666 12

The extracellular domain of the human leptin receptor (Ob-R) contains 20 potential N-glycosylation sites whose role in leptin binding remains to be elucidated. We found that a mammalian cell-expressed sOb-R (soluble Ob-R) fragment (residues 22-839 of the extracellular domain) bound leptin with a dissociation constant of 1.8 nM. This binding was inhibited by Con A (concanavalin A) or wheatgerm agglutinin. Treatment of sOb-R with peptide N-glycosidase F reduced leptin binding by approximately 80% concurrently with N-linked glycan removal. The human megakaryoblastic cell line, MEG-01, expresses two forms of the Ob-R, of approx. 170 and 130 kDa molecular mass. Endo H (endoglycosidase H) treatment and cell culture with alpha-glucosidase inhibitors demonstrated that N-linked glycans are of the complex mature type in the 170 kDa form and of the high-mannose type in the 130 kDa form. Both isoforms bound leptin, but not after peptide N-glycosidase F treatment. An insect-cell-expressed sOb-R fragment, consisting of the Ig (immunoglobulin), CRH2 (second cytokine receptor homology) and FNIII (fibronectin type III) domains, bound leptin with affinity similar to that of the entire extracellular domain, but this function was abolished after N-linked glycan removal. The same treatment had no effect on the leptin-binding activity of the isolated CRH2 domain. Our findings show that N-linked glycans within Ig and/or FNIII domains regulate Ob-R function, but are not involved in essential interactions with the ligand.
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PMID:Contribution of leptin receptor N-linked glycans to leptin binding. 1798 56

Blood coagulation factor VIII (FVIII) is a key cofactor in regulation of blood coagulation. This study investigated the mechanism by which FVIII is translated and transported into the endoplasmic reticulum (ER) and processed in the Golgi apparatus before secretion using an in vitro cell model. HEK-293T cells were transfected with vectors carrying wild-type (WT) FVIII or polymorphic FVIII D1241E for coexpression with ER lectins and treatment with tunicamycin (an N-linked glycosylation inhibitor), 1-deoxynojirimycin (an alpha-glucosidase inhibitor), endoglycosidase H, or MG132 (Cbz-Leu-Leu-leucinal; a proteasome inhibitor). The data showed that the minor allele of FVIII D1241E was able to reduce FVIII secretion into the conditioned medium but maintain a normal level of procoagulation ability, although both FVIII WT and the minor allele of FVIII D1241E showed similar levels of transcription and translation capacities. Functionally, the D1241E polymorphism led to a reduced level of FVIII in the Golgi apparatus because of its reduced association with malectin, which interacts with newly synthesized glycoproteins in the ER for FVIII folding and trafficking, leading to degradation of the minor allele of FVIII D1241E in the cytosol. This study demonstrated that malectin is important for regulation of the FVIII posttranslational process and that the minor allele of FVIII D1241E had a reduced association with malectin but an increased capacity for proteasomal FVIII degradation. These data imply the role of the ER quality control in future recombinant FVIII development.
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PMID:Blood coagulation factor VIII D1241E polymorphism leads to a weak malectin interaction and reduction of factor VIII posttranslational modification and secretion. 3314 78


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