Dominant: Negative Mutants of a Toxin Subunit: An Approach to Therapy of Anthrax

The protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes. We identified dominant-negative mutants of protective antigen that co-assemble with the...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2001-04, Vol.292 (5517), p.695-697
Main Authors: Sellman, Bret R., Mourez, Michael, Collier, R. John
Format: Article
Language:English
Subjects:
Animals
Anthrax
Anthrax - drug therapy
Antigens
Antigens, Bacterial
Bacillus anthracis
Bacterial Toxins - antagonists & inhibitors
Bacterial Toxins - genetics
Bacterial Toxins - metabolism
Bacterial Toxins - toxicity
Biochemistry
Biological and medical sciences
Biotechnology
Cell Membrane - metabolism
CHO Cells
Cricetinae
Cytosol
Endocytosis
Enzymes
Fundamental and applied biological sciences. Psychology
Genes, Dominant
Health. Pharmaceutical industry
Industrial applications and implications. Economical aspects
Inhibition
Male
Membranes
Mutation
Neutrophils
Other active biomolecules
Production of active biomolecules
Protein synthesis
Protein Transport
Rats
Rats, Inbred F344
Receptors
Receptors, Peptide - metabolism
Toxins
Vaccination
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes. We identified dominant-negative mutants of protective antigen that co-assemble with the wild-type protein and block its ability to translocate the enzymic moieties across membranes. These mutants strongly inhibited toxin action in cell culture and in an animal intoxication model, suggesting that they could be useful in therapy of anthrax.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.109563