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...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2001-04, Vol.292 (5517), p.695-697 |
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| creator | Sellman, Bret R. Mourez, Michael Collier, R. John |
| description | 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. |
| doi_str_mv | 10.1126/science.109563 |
| format | Article |
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John</creator><creatorcontrib>Sellman, Bret R. ; Mourez, Michael ; Collier, R. John</creatorcontrib><description>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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.109563</identifier><identifier>PMID: 11326092</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>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</subject><ispartof>Science (American Association for the Advancement of Science), 2001-04, Vol.292 (5517), p.695-697</ispartof><rights>Copyright 2001 American Association for the Advancement of Science</rights><rights>2001 INIST-CNRS</rights><rights>COPYRIGHT 2001 American Association for the Advancement of Science</rights><rights>COPYRIGHT 2001 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science Apr 27, 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c839t-d1a280657c09cf74a9b41aa680ed0a250a243db260d194beb470a10d0a693d463</citedby><cites>FETCH-LOGICAL-c839t-d1a280657c09cf74a9b41aa680ed0a250a243db260d194beb470a10d0a693d463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3083540$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3083540$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,2884,2885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=955042$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11326092$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sellman, Bret R.</creatorcontrib><creatorcontrib>Mourez, Michael</creatorcontrib><creatorcontrib>Collier, R. John</creatorcontrib><title>Dominant: Negative Mutants of a Toxin Subunit: An Approach to Therapy of Anthrax</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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.</description><subject>Animals</subject><subject>Anthrax</subject><subject>Anthrax - drug therapy</subject><subject>Antigens</subject><subject>Antigens, Bacterial</subject><subject>Bacillus anthracis</subject><subject>Bacterial Toxins - antagonists & inhibitors</subject><subject>Bacterial Toxins - genetics</subject><subject>Bacterial Toxins - metabolism</subject><subject>Bacterial Toxins - toxicity</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cell Membrane - metabolism</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cytosol</subject><subject>Endocytosis</subject><subject>Enzymes</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes, Dominant</subject><subject>Health. Pharmaceutical industry</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Inhibition</subject><subject>Male</subject><subject>Membranes</subject><subject>Mutation</subject><subject>Neutrophils</subject><subject>Other active biomolecules</subject><subject>Production of active biomolecules</subject><subject>Protein synthesis</subject><subject>Protein Transport</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Receptors</subject><subject>Receptors, Peptide - metabolism</subject><subject>Toxins</subject><subject>Vaccination</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0s2LEzEUAPAgitutXj2JDArqYacmk_mKt1q1LtStsNVreJPJtCnTpCaZpfvfm6FlpVKkhJCQ98v3Q-gFwSNCkvyDE0pqIUcEsyynj9Cg78QswfQxGmBM87jERXaBLp1bYxxijD5FF4TQJMcsGaAfn81GadD-Y3Qjl-DVnYy-dz4MuMg0EUQLs1M6uu2qTquAxjoab7fWgFhF3kSLlbSwve_pWPuVhd0z9KSB1snnh3aIfn79sph8i2fz6fVkPItFSZmPawJJifOsEJiJpkiBVSkByEssawxJFmpK6yqcsiYsrWSVFhgIDrGc0TrN6RC9268bDvO7k87zjXJCti1oaTrHi5SSvGChGaK3_5WkKDNGCAvw9T9wbTqrwy14QmhWhAfuV7vaoyW0kivdGG9BLKUOD9EaLRsVhsdFRvKwfc_jEzyUWm6UOOXfH_lAvNz5JXTO8evbm7Pp_NfZ9NP0XFpOZ0f06hQVpm3lUvLw3ZP5ER_tubDGOSsbvrVqA_aeE8z7ZOaHZOb7ZA4TXh3-o6s2sv7LD9kbwJsDACegbSxoodyDY1mG01693Ku188Y-RCkuaZZi-gfYAf9H</recordid><startdate>20010427</startdate><enddate>20010427</enddate><creator>Sellman, Bret R.</creator><creator>Mourez, Michael</creator><creator>Collier, R. 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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.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>11326092</pmid><doi>10.1126/science.109563</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2001-04, Vol.292 (5517), p.695-697 |
| issn | 0036-8075 1095-9203 |
| language | eng |
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| source | MEDLINE; Science Magazine; JSTOR Archive Collection A-Z Listing |
| 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 |
| title | Dominant: Negative Mutants of a Toxin Subunit: An Approach to Therapy of Anthrax |
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