Pertussis Toxin S1 Mutant with Reduced Enzyme Activity and a Conserved Protective Epitope
Pertussis toxin (PTX) is a major virulence factor in whooping cough and can elicit protective antibodies. Amino acid residues 8 to 15 of PTX subunit S1 are important for the adenosine diphosphate-ribosyltransferase activity associated with the pathobiological effects of PTX. Furthermore, this region...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1988-10, Vol.242 (4875), p.72-74 |
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| container_issue | 4875 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Burnette, W. Neal Cieplak, Witold Mar, Vernon L. Kaljot, Kaarel T. Sato, Hiroko Keith, Jerry M. |
| description | Pertussis toxin (PTX) is a major virulence factor in whooping cough and can elicit protective antibodies. Amino acid residues 8 to 15 of PTX subunit S1 are important for the adenosine diphosphate-ribosyltransferase activity associated with the pathobiological effects of PTX. Furthermore, this region contains at least a portion of an epitope that elicits both toxin-neutralizing and protective antibody responses in mice. The gene encoding the S1 subunit was subjected to site-specific mutagenesis in this critical region. A mutant containing a single amino acid substitution (Arg$^{9}\rightarrow $ Lys) had reduced enzymatic activity (approximately 0.02% of control) while retaining the protective epitope. This analog S1 molecule may provide the basis for a genetically detoxified PTX with potential for use as a component of an acellular vaccine against whooping cough. |
| doi_str_mv | 10.1126/science.2459776 |
| format | Article |
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Neal ; Cieplak, Witold ; Mar, Vernon L. ; Kaljot, Kaarel T. ; Sato, Hiroko ; Keith, Jerry M.</creator><creatorcontrib>Burnette, W. Neal ; Cieplak, Witold ; Mar, Vernon L. ; Kaljot, Kaarel T. ; Sato, Hiroko ; Keith, Jerry M.</creatorcontrib><description>Pertussis toxin (PTX) is a major virulence factor in whooping cough and can elicit protective antibodies. Amino acid residues 8 to 15 of PTX subunit S1 are important for the adenosine diphosphate-ribosyltransferase activity associated with the pathobiological effects of PTX. Furthermore, this region contains at least a portion of an epitope that elicits both toxin-neutralizing and protective antibody responses in mice. The gene encoding the S1 subunit was subjected to site-specific mutagenesis in this critical region. A mutant containing a single amino acid substitution (Arg$^{9}\rightarrow $ Lys) had reduced enzymatic activity (approximately 0.02% of control) while retaining the protective epitope. This analog S1 molecule may provide the basis for a genetically detoxified PTX with potential for use as a component of an acellular vaccine against whooping cough.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.2459776</identifier><identifier>PMID: 2459776</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: The American Association for the Advancement of Science</publisher><subject>adenosine diphosphate-ribosyltransferase ; Amino acids ; Antibodies ; Bacteriology ; Base Sequence ; Biological and medical sciences ; Bordetella pertussis ; Bordetella pertussis - enzymology ; Bordetella pertussis - genetics ; Codon ; Enzyme activity ; Epitopes ; Epitopes - genetics ; Fundamental and applied biological sciences. Psychology ; Genes ; Genes, Bacterial ; Genetic mutation ; Inclusion bodies ; Microbiology ; Mutation ; Mutation (Biology) ; NAD+ Nucleosidase - genetics ; NAD+ Nucleosidase - metabolism ; Operon ; Pertussis Toxin ; Poly(ADP-ribose) Polymerases - genetics ; Poly(ADP-ribose) Polymerases - metabolism ; Recombinant Proteins - metabolism ; site-directed mutagenesis ; Toxicity ; Toxins ; Vaccination ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies ; Virulence Factors, Bordetella - genetics ; Virulence Factors, Bordetella - immunology ; Virulence Factors, Bordetella - metabolism ; Whooping cough</subject><ispartof>Science (American Association for the Advancement of Science), 1988-10, Vol.242 (4875), p.72-74</ispartof><rights>Copyright 1988 The American Association for the Advancement of Science</rights><rights>1989 INIST-CNRS</rights><rights>COPYRIGHT 1988 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1988 American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c639t-7d9e8055cfcfda68911b0202d1840d76d1c2024582cb3ba7fb43cabfd0db764f3</citedby><cites>FETCH-LOGICAL-c639t-7d9e8055cfcfda68911b0202d1840d76d1c2024582cb3ba7fb43cabfd0db764f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/1702497$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/1702497$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=6984401$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2459776$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Burnette, W. Neal</creatorcontrib><creatorcontrib>Cieplak, Witold</creatorcontrib><creatorcontrib>Mar, Vernon L.</creatorcontrib><creatorcontrib>Kaljot, Kaarel T.</creatorcontrib><creatorcontrib>Sato, Hiroko</creatorcontrib><creatorcontrib>Keith, Jerry M.</creatorcontrib><title>Pertussis Toxin S1 Mutant with Reduced Enzyme Activity and a Conserved Protective Epitope</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Pertussis toxin (PTX) is a major virulence factor in whooping cough and can elicit protective antibodies. Amino acid residues 8 to 15 of PTX subunit S1 are important for the adenosine diphosphate-ribosyltransferase activity associated with the pathobiological effects of PTX. Furthermore, this region contains at least a portion of an epitope that elicits both toxin-neutralizing and protective antibody responses in mice. The gene encoding the S1 subunit was subjected to site-specific mutagenesis in this critical region. A mutant containing a single amino acid substitution (Arg$^{9}\rightarrow $ Lys) had reduced enzymatic activity (approximately 0.02% of control) while retaining the protective epitope. This analog S1 molecule may provide the basis for a genetically detoxified PTX with potential for use as a component of an acellular vaccine against whooping cough.</description><subject>adenosine diphosphate-ribosyltransferase</subject><subject>Amino acids</subject><subject>Antibodies</subject><subject>Bacteriology</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Bordetella pertussis</subject><subject>Bordetella pertussis - enzymology</subject><subject>Bordetella pertussis - genetics</subject><subject>Codon</subject><subject>Enzyme activity</subject><subject>Epitopes</subject><subject>Epitopes - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes</subject><subject>Genes, Bacterial</subject><subject>Genetic mutation</subject><subject>Inclusion bodies</subject><subject>Microbiology</subject><subject>Mutation</subject><subject>Mutation (Biology)</subject><subject>NAD+ Nucleosidase - genetics</subject><subject>NAD+ Nucleosidase - metabolism</subject><subject>Operon</subject><subject>Pertussis Toxin</subject><subject>Poly(ADP-ribose) Polymerases - genetics</subject><subject>Poly(ADP-ribose) Polymerases - metabolism</subject><subject>Recombinant Proteins - metabolism</subject><subject>site-directed mutagenesis</subject><subject>Toxicity</subject><subject>Toxins</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies</subject><subject>Virulence Factors, Bordetella - genetics</subject><subject>Virulence Factors, Bordetella - immunology</subject><subject>Virulence Factors, Bordetella - metabolism</subject><subject>Whooping cough</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0s9v0zAUB_AIgUYZnLmA5MMEh9HNzg87PpaqK5MKndhA4hQ59kvxlNjFdsa6vx5PjbYh9VD5YNnfj23J7yXJW4JPCEnpqZcajISTNC84Y_RZMiKYF2Oe4ux5MsI4o-MSs-Jl8sr7a4xjxrOD5GDgo-TXBbjQe689urK32qBLgr72QZiA_urwG30H1UtQaGbuNh2giQz6RocNEkYhgabWeHA3Mb9wNsB9CGi21sGu4XXyohGthzfDfJj8OJtdTb-MF8v5-XSyGEua8TBmikOJi0I2slGClpyQGqc4VaTMsWJUERlXeVGmss5qwZo6z6SoG4VVzWjeZIfJh-29a2f_9OBD1WkvoW2FAdv7ihSYE0Z4hMdbuBItVNo0NjghV2DAidYaaHTcnlCW5TmnUX_aoeNQ0Gm5g3_8j0cR4DasRPzb6vzy275y-XNf-Xm-pyzni6fyeJeUtm1hBVWszHT5VJ9utXTWewdNtXa6E25TEVzd91819F81NFQ88X6oRl93oB78Y3405MJL0TZOGKn9A6O8zHNMInu3Zdc-WPf4KoutwFn2D30o6lc</recordid><startdate>19881007</startdate><enddate>19881007</enddate><creator>Burnette, W. Neal</creator><creator>Cieplak, Witold</creator><creator>Mar, Vernon L.</creator><creator>Kaljot, Kaarel T.</creator><creator>Sato, Hiroko</creator><creator>Keith, Jerry M.</creator><general>The American Association for the Advancement of Science</general><general>American Association for the Advancement of Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8GL</scope><scope>IBG</scope><scope>IOV</scope><scope>ISN</scope><scope>7QL</scope><scope>7QO</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>19881007</creationdate><title>Pertussis Toxin S1 Mutant with Reduced Enzyme Activity and a Conserved Protective Epitope</title><author>Burnette, W. Neal ; Cieplak, Witold ; Mar, Vernon L. ; Kaljot, Kaarel T. ; Sato, Hiroko ; Keith, Jerry M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c639t-7d9e8055cfcfda68911b0202d1840d76d1c2024582cb3ba7fb43cabfd0db764f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>adenosine diphosphate-ribosyltransferase</topic><topic>Amino acids</topic><topic>Antibodies</topic><topic>Bacteriology</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Bordetella pertussis</topic><topic>Bordetella pertussis - enzymology</topic><topic>Bordetella pertussis - genetics</topic><topic>Codon</topic><topic>Enzyme activity</topic><topic>Epitopes</topic><topic>Epitopes - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes</topic><topic>Genes, Bacterial</topic><topic>Genetic mutation</topic><topic>Inclusion bodies</topic><topic>Microbiology</topic><topic>Mutation</topic><topic>Mutation (Biology)</topic><topic>NAD+ Nucleosidase - genetics</topic><topic>NAD+ Nucleosidase - metabolism</topic><topic>Operon</topic><topic>Pertussis Toxin</topic><topic>Poly(ADP-ribose) Polymerases - genetics</topic><topic>Poly(ADP-ribose) Polymerases - metabolism</topic><topic>Recombinant Proteins - metabolism</topic><topic>site-directed mutagenesis</topic><topic>Toxicity</topic><topic>Toxins</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies</topic><topic>Virulence Factors, Bordetella - genetics</topic><topic>Virulence Factors, Bordetella - immunology</topic><topic>Virulence Factors, Bordetella - metabolism</topic><topic>Whooping cough</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Burnette, W. Neal</creatorcontrib><creatorcontrib>Cieplak, Witold</creatorcontrib><creatorcontrib>Mar, Vernon L.</creatorcontrib><creatorcontrib>Kaljot, Kaarel T.</creatorcontrib><creatorcontrib>Sato, Hiroko</creatorcontrib><creatorcontrib>Keith, Jerry M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: High School</collection><collection>Gale In Context: Biography</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Burnette, W. Neal</au><au>Cieplak, Witold</au><au>Mar, Vernon L.</au><au>Kaljot, Kaarel T.</au><au>Sato, Hiroko</au><au>Keith, Jerry M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pertussis Toxin S1 Mutant with Reduced Enzyme Activity and a Conserved Protective Epitope</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>1988-10-07</date><risdate>1988</risdate><volume>242</volume><issue>4875</issue><spage>72</spage><epage>74</epage><pages>72-74</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Pertussis toxin (PTX) is a major virulence factor in whooping cough and can elicit protective antibodies. Amino acid residues 8 to 15 of PTX subunit S1 are important for the adenosine diphosphate-ribosyltransferase activity associated with the pathobiological effects of PTX. Furthermore, this region contains at least a portion of an epitope that elicits both toxin-neutralizing and protective antibody responses in mice. The gene encoding the S1 subunit was subjected to site-specific mutagenesis in this critical region. A mutant containing a single amino acid substitution (Arg$^{9}\rightarrow $ Lys) had reduced enzymatic activity (approximately 0.02% of control) while retaining the protective epitope. This analog S1 molecule may provide the basis for a genetically detoxified PTX with potential for use as a component of an acellular vaccine against whooping cough.</abstract><cop>Washington, DC</cop><pub>The American Association for the Advancement of Science</pub><pmid>2459776</pmid><doi>10.1126/science.2459776</doi><tpages>3</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1988-10, Vol.242 (4875), p.72-74 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_15091719 |
| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | adenosine diphosphate-ribosyltransferase Amino acids Antibodies Bacteriology Base Sequence Biological and medical sciences Bordetella pertussis Bordetella pertussis - enzymology Bordetella pertussis - genetics Codon Enzyme activity Epitopes Epitopes - genetics Fundamental and applied biological sciences. Psychology Genes Genes, Bacterial Genetic mutation Inclusion bodies Microbiology Mutation Mutation (Biology) NAD+ Nucleosidase - genetics NAD+ Nucleosidase - metabolism Operon Pertussis Toxin Poly(ADP-ribose) Polymerases - genetics Poly(ADP-ribose) Polymerases - metabolism Recombinant Proteins - metabolism site-directed mutagenesis Toxicity Toxins Vaccination Vaccines Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies Virulence Factors, Bordetella - genetics Virulence Factors, Bordetella - immunology Virulence Factors, Bordetella - metabolism Whooping cough |
| title | Pertussis Toxin S1 Mutant with Reduced Enzyme Activity and a Conserved Protective Epitope |
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