Calystegine B3 as a specific inhibitor for cytoplasmic alpha-mannosidase, Man2C1.

@article{Kato2011CalystegineBA,
  title={Calystegine B3 as a specific inhibitor for cytoplasmic alpha-mannosidase, Man2C1.},
  author={Atsushi Kato and Li Wang and Kumiko Ishii and Junichi Seino and Naoki Asano and Tadashi Suzuki},
  journal={Journal of biochemistry},
  year={2011},
  volume={149 4},
  pages={
          415-22
        }
}
Cytoplasmic α-mannosidase (Man2C1) has been implicated in non-lysosomal catabolism of free oligosaccharides derived from N-linked glycans accumulated in the cytosol. Suppression of Man2C1 expression reportedly induces apoptosis in various cell lines, but its molecular mechanism remains unclear. Development of a specific inhibitor for Man2C1 is critical to understanding its biological significance. In this study, we identified a plant-derived alkaloid, calystegine B(3), as a potent specific… Expand
Dual Functions for Cytosolic α-Mannosidase (Man2C1)
TLDR
It is demonstrated that silencing of Man2C1 via small hairpin RNAs induced mitochondria-dependent apoptosis in HeLa cells, demonstrating that the role of Man 2C1 in apoptosis is independent of its α-mannosidase activity. Expand
Metabolism of free oligosaccharides is facilitated in the och1Δ mutant of Saccharomyces cerevisiae.
TLDR
The results provide an insight into a possible link between catabolism of fOSs and cell wall stress. Expand
Basal Autophagy Is Required for the Efficient Catabolism of Sialyloligosaccharides*
TLDR
A surprising link between basal autophagy and catabolism of N-linked glycans is provided, showing that in Atg5−/− cells, sialyloligosaccharides specifically accumulated in the cytosol. Expand
Cytosolic Free N-Glycans Are Retro-Transported Into the Endoplasmic Reticulum in Plant Cells
TLDR
Analysis of the structures of free oligosaccharides in plant microsomes proved that HMT-FNGs could be found in microsome, which almost consist of the ER compartments, and found the presence of plant complex type (PCT)-GN1-F NGs, which carry the Lewisa epitope at the non-reducing end, indicating that these FNGs had been fully processed in the Golgi apparatus. Expand
Synthesis and biological evaluation of N-(2-fluorophenyl)-2β-deoxyfuconojirimycin acetamide as a potent inhibitor for α-l-fucosidases.
TLDR
It is noteworthy that the designed N-phenyl-2β-DFJ acetamide derivative exhibited about 18-fold stronger effects on human lysosomal α-l-fucosidase than original DFJ and it occupied the active-site of this enzyme, which means that this compound may find applications in new therapeutic trials against genetic deficiency disorders. Expand
Non-lysosomal degradation pathway for N-linked glycans and dolichol-linked oligosaccharides.
TLDR
The current knowledge of the molecular and regulatory mechanisms underlying the formation of fOSs and POSs in mammalian cells and Saccharomyces cerevisiae are summarized. Expand
Generation and degradation of free asparagine-linked glycans
TLDR
This article summarizes the current state of the authors' knowledge concerning the formation and catabolism of FNGs. Expand
Tailoring recombinant protein quality by rational media design
TLDR
The purpose of this review is to provide an overview of the way both classical cell culture medium components and novel supplements affect the quality attributes of recombinant therapeutic proteins expressed in mammalian hosts, allowing rational and high‐throughput optimization of mammalian cell culture media. Expand
Concise synthesis of calystegines B2 and B3via intramolecular Nozaki-Hiyama-Kishi reaction.
The key step in the concise syntheses of calystegine B2 and its C-2 epimer calystegine B3 was the construction of cycloheptanone 8via an intramolecular Nozaki-Hiyama-Kishi (NHK) reaction of 9, anExpand
Executing and rationalizing the synthesis of a difluorinated analogue of a ring-expanded calystegine B2.
TLDR
A difluorinated analogue of a ring-expanded calystegine B(2) and some N-protected species were prepared via microwave-mediated transannular ring-opening of an epoxyketone via density functional theory (DFT) methods to study the diastereofacial selectivity of the epoxidation reaction. Expand
...
1
2
...

References

SHOWING 1-10 OF 50 REFERENCES
Novel mannosidase inhibitors probe glycoprotein degradation pathways in cells
TLDR
This study delineated α-mannosidases hydrolytic pathways in azepane inhibitor treated cells by the analysis of free oligosaccharides (FOS) as markers of endoplasmic reticulum (ER), Golgi, lysosomal and cytosolic α-mannosidase activities and identified two compounds as potent and selective cytosol α- Mannosidase inhibitors. Expand
Man2C1, an α-mannosidase, is involved in the trimming of free oligosaccharides in the cytosol
TLDR
The findings in the present study demonstrate that an α-mannosidase, Man2C1, is involved in the processing of free oligosaccharides that are formed in the cytosol, and may represent the common ‘non-lysosomal’ catabolic pathway for N-glycans in animal cells, although the molecular mechanism as well as the functional importance of such processes remains to be determined. Expand
Cloning and expression of mouse cytosolic alpha-mannosidase (Man2c1).
TLDR
This enzyme activity was stimulated by cobalt and inhibited by DIM and EDTA, and it was demonstrated that the expressed enzyme was active towards the radiolabeled substrate Man9GlcNAc1 giving the final product Man5Glc NAc1 through the formation of Man8Glcnac1 isomer C as intermediate. Expand
Mammalian α-mannosidases—multiple forms but a common purpose?
Previously, alpha-mannosidases were classified as enzymes that process newly formed N-glycans or degrade mature glycoproteins. In this review, we suggest that two endoplasmic reticulum (ER)Expand
Evidence for an Essential Deglycosylation-Independent Activity of PNGase in Drosophila melanogaster
TLDR
Pngl was shown to be inevitable for the proper developmental transition and the biochemical properties other than deglycosylation activity is important for its biological function. Expand
Structural diversity of cytosolic free oligosaccharides in the human hepatoma cell line, HepG2.
TLDR
The presence of the series "2" oligosaccharides suggests that some of the misfolded glycoproteins had been processed in pre-cis-Golgi vesicles and/or the Golgi apparatus. Expand
Endo-β-N-acetylglucosaminidase, an enzyme involved in processing of free oligosaccharides in the cytosol
TLDR
The identification of the gene encoding human cytosolic ENGase, a key enzyme involved in the processing of free oligosaccharides in the cytosol, was reported, suggesting that this enzyme is involved in basic biological processes in eukaryotic cells. Expand
Substrate specificities of rat kidney lysosomal and cytosolic alpha-D-mannosidases and effects of swainsonine suggest a role of the cytosolic enzyme in glycoprotein catabolism.
TLDR
It is reported that swainsonine administration in the rat is different in two respects from those found in other animals thus far studied, and results point to possible involvement of cytosolic alpha-D-mannosidase in glycoprotein degradation in theRat. Expand
Characterization and subcellular localization of human neutral class IIα-mannosidase cytosolic enzymes/free oligosaccharides/glycosidehydrolase family 38/M2C1/N-glycosylation
TLDR
The findings from enzyme-substrate characterizations and subcellular localization studies support the suggested role for neutral alpha-mannosidase in hydrolysis of soluble cytosolic oligomannosides. Expand
Cytoplasmic peptide:N‐glycanase (PNGase) in eukaryotic cells: occurrence, primary structure, and potential functions
TLDR
The primary structure and potential functions of the cytoplasmic PNGases are reviewed and a mouse homologue of Png1p bound not only to the Rad23 protein, but also to various proteins related to ubiquitin and/or the proteasome through an extended amino‐terminal domain. Expand
...
1
2
3
4
5
...