FASEB J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Elbein, A. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Elbein, A. D.

The FASEB Journal, Vol 5, 3055-3063, Copyright © 1991 by The Federation of American Societies for Experimental Biology

REVIEWS

Glycosidase inhibitors: inhibitors of N-linked oligosaccharide processing

AD Elbein
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock 72205.

The biosynthesis of the various types of N-linked oligosaccharide structures involves two series of reactions: 1) the formation of the lipid-linked saccharide precursor, Glc3Man9(GlcNAc)2-pyrophosphoryl- dolichol, by the stepwise addition of GlcNAc, mannose and glucose to dolichyl-P, and 2) the removal of glucose and mannose by membrane-bound glycosidases and the addition of GlcNAc, galactose, sialic acid, and fucose by Golgi-localized glycosyltransferases to produce different complex oligosaccharide structures. For most glycoproteins, the precise role of the carbohydrate is still not known, but specific N-linked oligosaccharide structures are key players in targeting of lysosomal hydrolases to the lysosomes, in the clearance of asialoglycoproteins from the serum, and in some cases of cell:cell adhesion. Furthermore, many glycoproteins have more than one N-linked oligosaccharide, and these oligosaccharides on the same protein frequently have different structures. Thus, one oligosaccharide may be of the high-mannose type whereas another may be a complex chain. One approach to determining the role of specific structures in glycoprotein function is to use inhibitors that block the modification reactions at different steps, causing the cell to produce glycoproteins with altered carbohydrate structures. The function of these glycoproteins can then be assessed. A number of alkaloid-like compounds have been identified that are specific inhibitors of the glucosidases and mannosidases involved in glycoprotein processing. These compounds cause the formation of glycoproteins with glucose-containing high mannose structures, or various high-mannose or hybrid chains, depending on the site of inhibition. These inhibitors have also been useful for studying the processing pathway and for comparing processing enzymes from different organisms.


This article has been cited by other articles:


Home page
 J. Exp. Med.Home page
G. Vogt, J. Bustamante, A. Chapgier, J. Feinberg, S. Boisson Dupuis, C. Picard, N. Mahlaoui, L. Gineau, A. Alcais, C. Lamaze, et al.
Complementation of a pathogenic IFNGR2 misfolding mutation with modifiers of N-glycosylation
J. Exp. Med., August 4, 2008; 205(8): 1729 - 1737.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
E. Ferraro, A. Pulicati, M. T. Cencioni, M. Cozzolino, F. Navoni, S. di Martino, R. Nardacci, M. T. Carri, and F. Cecconi
Apoptosome-deficient Cells Lose Cytochrome c through Proteasomal Degradation but Survive by Autophagy-dependent Glycolysis
Mol. Biol. Cell, August 1, 2008; 19(8): 3576 - 3588.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Magnelli, J. F. Cipollo, D. M. Ratner, J. Cui, D. Kelleher, R. Gilmore, C. E. Costello, P. W. Robbins, and J. Samuelson
Unique Asn-linked Oligosaccharides of the Human Pathogen Entamoeba histolytica
J. Biol. Chem., June 27, 2008; 283(26): 18355 - 18364.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
D. Yamaguchi, N. Kawasaki, I. Matsuo, K. Totani, H. Tozawa, N. Matsumoto, Y. Ito, and K. Yamamoto
VIPL has sugar-binding activity specific for high-mannose-type N-glycans, and glucosylation of the {alpha}1,2 mannotriosyl branch blocks its binding
Glycobiology, October 1, 2007; 17(10): 1061 - 1069.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. B. Free, L. A. Hazelwood, D. M. Cabrera, H. N. Spalding, Y. Namkung, M. L. Rankin, and D. R. Sibley
D1 and D2 Dopamine Receptor Expression Is Regulated by Direct Interaction with the Chaperone Protein Calnexin
J. Biol. Chem., July 20, 2007; 282(29): 21285 - 21300.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Banerjee, P. Vishwanath, J. Cui, D. J. Kelleher, R. Gilmore, P. W. Robbins, and J. Samuelson
The evolution of N-glycan-dependent endoplasmic reticulum quality control factors for glycoprotein folding and degradation
PNAS, July 10, 2007; 104(28): 11676 - 11681.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
A. Angelov, M. Putyrski, and W. Liebl
Molecular and Biochemical Characterization of {alpha}-Glucosidase and {alpha}-Mannosidase and Their Clustered Genes from the Thermoacidophilic Archaeon Picrophilus torridus.
J. Bacteriol., October 1, 2006; 188(20): 7123 - 7131.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
T. Pulinilkunnil and B. Rodrigues
Cardiac lipoprotein lipase: Metabolic basis for diabetic heart disease
Cardiovasc Res, February 1, 2006; 69(2): 329 - 340.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
V. P. Mishin, D. Novikov, F. G. Hayden, and L. V. Gubareva
Effect of Hemagglutinin Glycosylation on Influenza Virus Susceptibility to Neuraminidase Inhibitors
J. Virol., October 1, 2005; 79(19): 12416 - 12424.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
T. D. Butters, R. A. Dwek, and F. M. Platt
Imino sugar inhibitors for treating the lysosomal glycosphingolipidoses
Glycobiology, October 1, 2005; 15(10): 43R - 52R.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Flores-Diaz, A. Alape-Giron, G. Clark, B. Catimel, Y. Hirabayashi, E. Nice, J.-M. Gutierrez, R. Titball, and M. Thelestam
A Cellular Deficiency of Gangliosides Causes Hypersensitivity to Clostridium perfringens Phospholipase C
J. Biol. Chem., July 22, 2005; 280(29): 26680 - 26689.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S. Svedine, T. Wang, R. Halaban, and D. N. Hebert
Carbohydrates act as sorting determinants in ER-associated degradation of tyrosinase
J. Cell Sci., June 15, 2004; 117(14): 2937 - 2949.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
X. Shi and R. M. Elliott
Analysis of N-Linked Glycosylation of Hantaan Virus Glycoproteins and the Role of Oligosaccharide Side Chains in Protein Folding and Intracellular Trafficking
J. Virol., May 15, 2004; 78(10): 5414 - 5422.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. B. Tropak, S. P. Reid, M. Guiral, S. G. Withers, and D. Mahuran
Pharmacological Enhancement of {beta}-Hexosaminidase Activity in Fibroblasts from Adult Tay-Sachs and Sandhoff Patients
J. Biol. Chem., April 2, 2004; 279(14): 13478 - 13487.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Mancini, M. Aebi, and A. Helenius
Multiple Endoplasmic Reticulum-associated Pathways Degrade Mutant Yeast Carboxypeptidase Y in Mammalian Cells
J. Biol. Chem., November 21, 2003; 278(47): 46895 - 46905.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. A. Carlow, M. J. Williams, and H. J. Ziltener
Modulation of O-Glycans and N-Glycans on Murine CD8 T Cells Fails to Alter Annexin V Ligand Induction by Galectin 1
J. Immunol., November 15, 2003; 171(10): 5100 - 5106.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
N. Asano
Glycosidase inhibitors: update and perspectives on practical use
Glycobiology, October 1, 2003; 13(10): 93R - 104R.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Wu, M. T. Swulius, K. W. Moremen, and R. N. Sifers
Elucidation of the molecular logic by which misfolded {alpha}1-antitrypsin is preferentially selected for degradation
PNAS, July 8, 2003; 100(14): 8229 - 8234.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Garrigue-Antar, N. Hartigan, and K. E. Kadler
Post-translational Modification of Bone Morphogenetic Protein-1 Is Required for Secretion and Stability of the Protein
J. Biol. Chem., November 1, 2002; 277(45): 43327 - 43334.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
C. M. Cabral, Y. Liu, K. W. Moremen, and R. N. Sifers
Organizational Diversity among Distinct Glycoprotein Endoplasmic Reticulum-associated Degradation Programs
Mol. Biol. Cell, August 1, 2002; 13(8): 2639 - 2650.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
M. Merola, M. Brazzoli, F. Cocchiarella, J. M. Heile, A. Helenius, A. J. Weiner, M. Houghton, and S. Abrignani
Folding of Hepatitis C Virus E1 Glycoprotein in a Cell-Free System
J. Virol., November 15, 2001; 75(22): 11205 - 11217.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
M. J. Spiro and R. G. Spiro
Release of polymannose oligosaccharides from vesicular stomatitis virus G protein during endoplasmic reticulum-associated degradation
Glycobiology, October 1, 2001; 11(10): 803 - 811.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. Helenius and M. Aebi
Intracellular Functions of N-Linked Glycans
Science, March 23, 2001; 291(5512): 2364 - 2369.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
B. Albrecht, M. Woisetschlager, and M. W. Robertson
Export of the High Affinity IgE Receptor From the Endoplasmic Reticulum Depends on a Glycosylation-Mediated Quality Control Mechanism
J. Immunol., November 15, 2000; 165(10): 5686 - 5694.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
L. L. Christensen, U. B. Jensen, P. Bross, and T. F. Orntoft
The C-terminal N-glycosylation sites of the human {alpha}1,3/4-fucosyltransferase III, -V, and -VI (hFucTIII, -V and -VI) are necessary for the expression of full enzyme activity
Glycobiology, September 1, 2000; 10(9): 931 - 939.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
M. F. Pelletier, A. Marcil, G. Sevigny, C. A. Jakob, D. C. Tessier, E. Chevet, R. Menard, J. J.M. Bergeron, and D. Y. Thomas
The heterodimeric structure of glucosidase II is required for its activity, solubility, and localization in vivo
Glycobiology, August 1, 2000; 10(8): 815 - 827.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
B. R.S. Ali and M. C. Field
Glycopeptide export from mammalian microsomes is independent of calcium and is distinct from oligosaccharide export
Glycobiology, April 1, 2000; 10(4): 383 - 391.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. H. Chung, K. Ohashi, M. Watanabe, N. Miyasaka, and S. Hirosawa
Mannose Trimming Targets Mutant alpha 2-Plasmin Inhibitor for Degradation by the Proteasome
J. Biol. Chem., February 18, 2000; 275(7): 4981 - 4987.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
W. T. Doerrler and M. A. Lehrman
Regulation of the dolichol pathway in human fibroblasts by the endoplasmic reticulum unfolded protein response
PNAS, November 9, 1999; 96(23): 13050 - 13055.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
M. Flamand, F. Megret, M. Mathieu, J. Lepault, F. A. Rey, and V. Deubel
Dengue Virus Type 1 Nonstructural Glycoprotein NS1 Is Secreted from Mammalian Cells as a Soluble Hexamer in a Glycosylation-Dependent Fashion
J. Virol., July 1, 1999; 73(7): 6104 - 6110.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
M. Popov and R. A. F. Reithmeier
Calnexin Interaction with N-Glycosylation Mutants of a Polytopic Membrane Glycoprotein, the Human Erythrocyte Anion Exchanger 1 (Band 3)
J. Biol. Chem., June 18, 1999; 274(25): 17635 - 17642.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Liu, P. Choudhury, C. M. Cabral, and R. N. Sifers
Oligosaccharide Modification in the Early Secretory Pathway Directs the Selection of a Misfolded Glycoprotein for Degradation by the Proteasome
J. Biol. Chem., February 26, 1999; 274(9): 5861 - 5867.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. J. Bennett, J. E. M. Van Leeuwen, and K. P. Kearse
Calnexin Association Is Not Sufficient to Protect T Cell Receptor alpha  Proteins from Rapid Degradation in CD4+CD8+ Thymocytes
J. Biol. Chem., September 11, 1998; 273(37): 23674 - 23680.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
W. H. Taylor, A. Sinha, I. A. Khan, S. T. McDaniel, and J. D. Esko
Primers of Glycosaminoglycan Biosynthesis from Peruvian Rain Forest Plants
J. Biol. Chem., August 28, 1998; 273(35): 22260 - 22266.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
M. Yang, S. Omura, J. S. Bonifacino, and A. M. Weissman
Novel Aspects of Degradation of T Cell Receptor Subunits from the Endoplasmic Reticulum (ER) in T Cells: Importance of Oligosaccharide Processing, Ubiquitination, and Proteasome-dependent Removal from ER Membranes
J. Exp. Med., March 16, 1998; 187(6): 835 - 846.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K.-W. Zhao, K. F. Faull, E. D. Kakkis, and E. F. Neufeld
Carbohydrate Structures of Recombinant Human alpha -L-Iduronidase Secreted by Chinese Hamster Ovary Cells
J. Biol. Chem., September 5, 1997; 272(36): 22758 - 22765.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. Grossmann, B. D. Weintraub, and M. W. Szkudlinski
Novel Insights into the Molecular Mechanisms of Human Thyrotropin Action: Structural, Physiological, and Therapeutic Implications for the Glycoprotein Hormone Family
Endocr. Rev., August 1, 1997; 18(4): 476 - 501.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Liu, P. Choudhury, C. M. Cabral, and R. N. Sifers
Intracellular Disposal of Incompletely Folded Human alpha 1-Antitrypsin Involves Release from Calnexin and Post-translational Trimming of Asparagine-linked Oligosaccharides
J. Biol. Chem., March 21, 1997; 272(12): 7946 - 7951.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. E.M. Van Leeuwen and K. P. Kearse
Reglucosylation of N-Linked Glycans Is Critical for Calnexin Assembly with T Cell Receptor (TCR) alpha Proteins but Not TCRbeta Proteins
J. Biol. Chem., February 14, 1997; 272(7): 4179 - 4186.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
U. Tatu and A. Helenius
Interactions between Newly Synthesized Glycoproteins, Calnexin and a Network of Resident Chaperones in the Endoplasmic Reticulum
J. Cell Biol., February 10, 1997; 136(3): 555 - 565.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Grossmann, R. Wong, N. G. Teh, J. E. Tropea, J. East-Palmer, B. D. Weintraub, and M. W. Szkudlinski
Expression of Biologically Active Human Thyrotropin (hTSH) in a Baculovirus System: Effect of Insect Cell Glycosylation on hTSH Activity in Vitro and in Vivo
Endocrinology, January 1, 1997; 138(1): 92 - 100.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. E.M. Van Leeuwen and K. P. Kearse
The Related Molecular Chaperones Calnexin and Calreticulin Differentially Associate with Nascent T Cell Antigen Receptor Proteins within the Endoplasmic Reticulum
J. Biol. Chem., October 11, 1996; 271(41): 25345 - 25349.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. S. Shtrom and Z. W. Hall
Formation of a Ligand-binding Site for the Acetylcholine Receptor in Vitro
J. Biol. Chem., October 11, 1996; 271(41): 25506 - 25514.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
E. R. Torre and O. Steward
Protein Synthesis within Dendrites: Glycosylation of Newly Synthesized Proteins in Dendrites of Hippocampal Neurons in Culture
J. Neurosci., October 1, 1996; 16(19): 5967 - 5978.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Sgroi, A. Nocks, and I. Stamenkovic
A Single N-linked Glycosylation Site Is Implicated in the Regulation of Ligand Recognition by the I-type Lectins CD22 and CD33
J. Biol. Chem., August 2, 1996; 271(31): 18803 - 18809.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. E. M. van Leeuwen and K. P. Kearse
Calnexin Associates Exclusively with Individual CD3[IMAGE] and T Cell Antigen Receptor (TCR) alpha Proteins Containing Incompletely Trimmed Glycans That Are Not Assembled into Multisubunit TCR Complexes
J. Biol. Chem., April 19, 1996; 271(16): 9660 - 9665.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. P. Balow, J. D. Weissman, and K. P. Kearse
Unique Expression of Major Histocompatibility Complex Class I Proteins in the Absence of Glucose Trimming and Calnexin Association
J. Biol. Chem., December 1, 1995; 270(48): 29025 - 29029.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
C Hammond and A Helenius
Folding of VSV G protein: sequential interaction with BiP and calnexin
Science, October 21, 1994; 266(5184): 456 - 458.
[Abstract] [PDF]

Home page
 J. Biol. Chem.Home page
A. Garami and T. Ilg
The Role of Phosphomannose Isomerase in Leishmania mexicana Glycoconjugate Synthesis and Virulence
J. Biol. Chem., February 23, 2001; 276(9): 6566 - 6575.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Fagioli and R. Sitia
Glycoprotein Quality Control in the Endoplasmic Reticulum. MANNOSE TRIMMING BY ENDOPLASMIC RETICULUM MANNOSIDASE I TIMES THE PROTEASOMAL DEGRADATION OF UNASSEMBLED IMMUNOGLOBULIN SUBUNITS
J. Biol. Chem., April 13, 2001; 276(16): 12885 - 12892.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. M. Cabral, P. Choudhury, Y. Liu, and R. N. Sifers
Processing by Endoplasmic Reticulum Mannosidases Partitions a Secretion-impaired Glycoprotein into Distinct Disposal Pathways
J. Biol. Chem., August 4, 2000; 275(32): 25015 - 25022.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. G. Spiro
Glucose Residues as Key Determinants in the Biosynthesis and Quality Control of Glycoproteins with N-Linked Oligosaccharides
J. Biol. Chem., November 10, 2000; 275(46): 35657 - 35660.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1991 by The Federation of American Societies for Experimental Biology.