Mannostatin A, a new glycoprotein-processing inhibitor

Journal Article · Mon Oct 01 04:00:00 EDT 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00495a008· OSTI ID:5674571

Tropea, J E; Kaushal, G P; Pastuszak, I; Mitchell, M; Elbein, A D ^[1]; Aoyagi, Takaaki ^[2]; Molyneux, R J ^[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)

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.

• OSTI ID: 5674571
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:43; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
AMINO ACIDS
BIOCHEMISTRY
CARBOHYDRATES
CARBOXYLIC ACIDS
CHEMISTRY
DOSE-RESPONSE RELATIONSHIPS
ENZYME INHIBITORS
ENZYMES
GLYCOPROTEINS
GLYCOSYL HYDROLASES
HEXOSES
HYDROGEN COMPOUNDS
HYDROLASES
INFLUENZA VIRUSES
LEUCINE
MANNOSE
METABOLITES
MICROORGANISMS
MONOSACCHARIDES
OLIGOSACCHARIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PARASITES
PROTEINS
SACCHARIDES
TRITIUM COMPOUNDS
VIRUSES