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Title: Mannostatin A, a new glycoprotein-processing inhibitor

Abstract

Mannostatin A is a metabolite produced by the microorganism Streptoverticillium verticillus and reported to be a potent competitive inhibitor of rat epididymal {alpha}-mannosidase. When tested against a number of other arylglycosidases, mannostatin A was inactive toward {alpha}- and {beta}-glucosidase and galactosidase as well as {beta}-mannosidase, but it was a potent inhibitor of jack bean, mung bean, and rat liver lysosomal {alpha}-mannosidases, with estimated IC{sub 50}'s of 70 nM, 450 nM, and 160 nM, respectively. The type of inhibition was competitive in nature. This compound also proved to be an effective competitive inhibitor of the glycoprotein-processing enzyme mannosidase II (IC{sub 50} of about 10-15 nM with p-nitrophenyl {alpha}-D-mannopyranoside as substrate, and about 90 nM with ({sup 3}H)mannose-labeled GlcNAc-Man{sub 5}GlcNAc as substrate). However, it was virtually inactive toward mannosidase I. The N-acetylated derivative of mannostatin A had no inhibitory activity. In cell culture studies, mannostatin A also proved to be a potent inhibitor of glycoprotein processing. Thus, in influenza virus infected Madin Darby canine kidney (MDCK) cells, mannostatin A blocked the normal formation of complex types of oligosaccharides on the viral glycoproteins and caused the accumulation of hybrid types of oligosaccharides. This observation is in keeping with other data which indicate thatmore » the site of action of mannostatin A is mannosidase II. Thus, mannostatin A represents the first nonalkaloidal processing inhibitor and adds to the growing list of chemical structures that can have important biological activity.« less

Authors:
; ; ; ;  [1];  [2];  [3]
  1. The Univ. of Texas Health Science Center, San Antonio (USA)
  2. The Microbial Chemistry Research Foundation, Shinagawa-ku, Tokyo (Japan)
  3. Western Regional Research Center, Berkeley, CA (USA)
Publication Date:
OSTI Identifier:
5674571
Resource Type:
Journal Article
Journal Name:
Biochemistry; (USA)
Additional Journal Information:
Journal Volume: 29:43; Journal ID: ISSN 0006-2960
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ENZYME INHIBITORS; DOSE-RESPONSE RELATIONSHIPS; GLYCOPROTEINS; BIOCHEMISTRY; MICROORGANISMS; METABOLITES; GLYCOSYL HYDROLASES; INFLUENZA VIRUSES; LEUCINE; MANNOSE; OLIGOSACCHARIDES; TRITIUM COMPOUNDS; ALDEHYDES; AMINO ACIDS; CARBOHYDRATES; CARBOXYLIC ACIDS; CHEMISTRY; ENZYMES; HEXOSES; HYDROGEN COMPOUNDS; HYDROLASES; MONOSACCHARIDES; ORGANIC ACIDS; ORGANIC COMPOUNDS; PARASITES; PROTEINS; SACCHARIDES; VIRUSES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Tropea, J E, Kaushal, G P, Pastuszak, I, Mitchell, M, Elbein, A D, Aoyagi, Takaaki, and Molyneux, R J. Mannostatin A, a new glycoprotein-processing inhibitor. United States: N. p., 1990. Web. doi:10.1021/bi00495a008.
Tropea, J E, Kaushal, G P, Pastuszak, I, Mitchell, M, Elbein, A D, Aoyagi, Takaaki, & Molyneux, R J. Mannostatin A, a new glycoprotein-processing inhibitor. United States. https://doi.org/10.1021/bi00495a008
Tropea, J E, Kaushal, G P, Pastuszak, I, Mitchell, M, Elbein, A D, Aoyagi, Takaaki, and Molyneux, R J. Mon . "Mannostatin A, a new glycoprotein-processing inhibitor". United States. https://doi.org/10.1021/bi00495a008.
@article{osti_5674571,
title = {Mannostatin A, a new glycoprotein-processing inhibitor},
author = {Tropea, J E and Kaushal, G P and Pastuszak, I and Mitchell, M and Elbein, A D and Aoyagi, Takaaki and Molyneux, R J},
abstractNote = {Mannostatin A is a metabolite produced by the microorganism Streptoverticillium verticillus and reported to be a potent competitive inhibitor of rat epididymal {alpha}-mannosidase. When tested against a number of other arylglycosidases, mannostatin A was inactive toward {alpha}- and {beta}-glucosidase and galactosidase as well as {beta}-mannosidase, but it was a potent inhibitor of jack bean, mung bean, and rat liver lysosomal {alpha}-mannosidases, with estimated IC{sub 50}'s of 70 nM, 450 nM, and 160 nM, respectively. The type of inhibition was competitive in nature. This compound also proved to be an effective competitive inhibitor of the glycoprotein-processing enzyme mannosidase II (IC{sub 50} of about 10-15 nM with p-nitrophenyl {alpha}-D-mannopyranoside as substrate, and about 90 nM with ({sup 3}H)mannose-labeled GlcNAc-Man{sub 5}GlcNAc as substrate). However, it was virtually inactive toward mannosidase I. The N-acetylated derivative of mannostatin A had no inhibitory activity. In cell culture studies, mannostatin A also proved to be a potent inhibitor of glycoprotein processing. Thus, in influenza virus infected Madin Darby canine kidney (MDCK) cells, mannostatin A blocked the normal formation of complex types of oligosaccharides on the viral glycoproteins and caused the accumulation of hybrid types of oligosaccharides. This observation is in keeping with other data which indicate that the site of action of mannostatin A is mannosidase II. Thus, mannostatin A represents the first nonalkaloidal processing inhibitor and adds to the growing list of chemical structures that can have important biological activity.},
doi = {10.1021/bi00495a008},
url = {https://www.osti.gov/biblio/5674571}, journal = {Biochemistry; (USA)},
issn = {0006-2960},
number = ,
volume = 29:43,
place = {United States},
year = {1990},
month = {10}
}