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Mannostatin A, a new glycoprotein-processing inhibitor.
J E Tropea1, G P Kaushal, I Pastuszak
1Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284.
Biochemistry
|October 30, 1990
Summary
Mannostatin A is a potent inhibitor of alpha-mannosidases, particularly mannosidase II, affecting glycoprotein processing. This discovery offers a new nonalkaloidal tool for studying biological pathways.
Area of Science:
- Biochemistry
- Enzymology
- Glycobiology
Background:
- Mannostatin A, a metabolite from Streptoverticillium verticillus, is identified as a potent competitive inhibitor.
- It specifically targets rat epididymal alpha-mannosidase and various lysosomal alpha-mannosidases.
Purpose of the Study:
- To investigate the inhibitory effects of Mannostatin A on different alpha-mannosidases.
- To determine its efficacy as a glycoprotein processing inhibitor in cell culture.
Main Methods:
- Enzyme inhibition assays were performed using various arylglycosidases and alpha-mannosidases.
- Cell culture studies involved influenza virus-infected Madin Darby canine kidney (MDCK) cells to observe glycoprotein processing.
Main Results:
- Mannostatin A showed potent competitive inhibition against jack bean, mung bean, and rat liver lysosomal alpha-mannosidases (IC50s 70-450 nM).
- It effectively inhibited mannosidase II (IC50 10-90 nM) but not mannosidase I.
- In MDCK cells, Mannostatin A blocked complex oligosaccharide formation and caused accumulation of hybrid types.
Conclusions:
- Mannostatin A is a highly specific and potent inhibitor of mannosidase II, a key enzyme in glycoprotein processing.
- It represents the first nonalkaloidal inhibitor of glycoprotein processing, offering a valuable research tool.