TOX1_BORPE
ID TOX1_BORPE Reviewed; 269 AA.
AC P04977; O69258; O70057; Q599G4; Q5EIB9; Q93V22;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Pertussis toxin subunit 1;
DE Short=PTX S1;
DE AltName: Full=Islet-activating protein S1;
DE Short=IAP S1;
DE AltName: Full=NAD-dependent ADP-ribosyltransferase;
DE EC=2.4.2.-;
DE Flags: Precursor;
GN Name=ptxA; OrderedLocusNames=BP3783;
OS Bordetella pertussis (strain Tohama I / ATCC BAA-589 / NCTC 13251).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Alcaligenaceae; Bordetella.
OX NCBI_TaxID=257313;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BP165;
RX PubMed=2873570; DOI=10.1073/pnas.83.13.4631;
RA Nicosia A., Perugini M., Franzini C., Casagli M.C., Borri M.G., Antoni G.,
RA Almoni M., Neri P., Ratti G., Rappuoli R.;
RT "Cloning and sequencing of the pertussis toxin genes: operon structure and
RT gene duplication.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:4631-4635(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=3779;
RX PubMed=3704651; DOI=10.1126/science.3704651;
RA Locht C., Keith J.M.;
RT "Pertussis toxin gene: nucleotide sequence and genetic organization.";
RL Science 232:1258-1264(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=10536;
RX PubMed=2554254; DOI=10.1093/nar/17.20.8365;
RA Loosmore S.M., Cunningham J.D., Bradley W.R., Yao E.L., Dekaban G.A.,
RA Klein M.H.;
RT "A unique sequence of the Bordetella pertussis toxin operon.";
RL Nucleic Acids Res. 17:8365-8365(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=B572, B592, and B6;
RX PubMed=9453625; DOI=10.1128/iai.66.2.670-675.1998;
RA Mooi F.R., van Oirschot H., Heuvelman K., van der Heide H.G., Gaastra W.,
RA Willems R.J.;
RT "Polymorphism in the Bordetella pertussis virulence factors P.69/pertactin
RT and pertussis toxin in The Netherlands: temporal trends and evidence for
RT vaccine-driven evolution.";
RL Infect. Immun. 66:670-675(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=18323, 287, Al1561, CZ, HAV, Tohama I / ATCC BAA-589 / NCTC 13251,
RC and Wellcome 28;
RX PubMed=10418915; DOI=10.1016/s0264-410x(99)00038-9;
RA Boursaux-Eude C., Thiberge S., Carletti G., Guiso N.;
RT "Intranasal murine model of Bordetella pertussis infection: II. Sequence
RT variation and protection induced by a tricomponent acellular vaccine.";
RL Vaccine 17:2651-2660(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CHANG;
RX PubMed=15061492; DOI=10.1017/s095026880300164x;
RA Poynten M., McIntyre P.B., Mooi F.R., Heuvelman G.L., Gilbert G.L.;
RT "Temporal trends in circulating Bordetella pertussis strains in
RT Australia.";
RL Epidemiol. Infect. 132:185-193(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CS;
RA Wang Y., Zhang S., Lei D.;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=134;
RA Mallya A.D., Kumar M., Reddy M.N., Seshubabu B., Deobagkar D.D.,
RA Kapre S.V.;
RT "Bordetella pertussis toxin gene encoding subunit S1.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tohama I / ATCC BAA-589 / NCTC 13251;
RX PubMed=12910271; DOI=10.1038/ng1227;
RA Parkhill J., Sebaihia M., Preston A., Murphy L.D., Thomson N.R.,
RA Harris D.E., Holden M.T.G., Churcher C.M., Bentley S.D., Mungall K.L.,
RA Cerdeno-Tarraga A.-M., Temple L., James K.D., Harris B., Quail M.A.,
RA Achtman M., Atkin R., Baker S., Basham D., Bason N., Cherevach I.,
RA Chillingworth T., Collins M., Cronin A., Davis P., Doggett J., Feltwell T.,
RA Goble A., Hamlin N., Hauser H., Holroyd S., Jagels K., Leather S.,
RA Moule S., Norberczak H., O'Neil S., Ormond D., Price C., Rabbinowitsch E.,
RA Rutter S., Sanders M., Saunders D., Seeger K., Sharp S., Simmonds M.,
RA Skelton J., Squares R., Squares S., Stevens K., Unwin L., Whitehead S.,
RA Barrell B.G., Maskell D.J.;
RT "Comparative analysis of the genome sequences of Bordetella pertussis,
RT Bordetella parapertussis and Bordetella bronchiseptica.";
RL Nat. Genet. 35:32-40(2003).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-64, AND DOMAIN.
RX PubMed=2455296; DOI=10.1073/pnas.85.13.4667;
RA Cieplak W., Burnette W.N., Mar V.L., Kaljot K.T., Morris C.F., Chen K.K.,
RA Sato H., Keith J.M.;
RT "Identification of a region in the S1 subunit of pertussis toxin that is
RT required for enzymatic activity and that contributes to the formation of a
RT neutralizing antigenic determinant.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:4667-4671(1988).
RN [11]
RP PROTEIN SEQUENCE OF 153-169, AND ACTIVE SITE.
RC STRAIN=10536;
RX PubMed=2737291; DOI=10.1016/0014-5793(89)80652-0;
RA Cockle S.A.;
RT "Identification of an active-site residue in subunit S1 of pertussis toxin
RT by photocrosslinking to NAD.";
RL FEBS Lett. 249:329-332(1989).
RN [12]
RP ROLE OF TRP-60.
RX PubMed=2551899; DOI=10.1016/s0021-9258(18)71495-6;
RA Cortina G., Barbieri J.T.;
RT "Role of tryptophan 26 in the NAD glycohydrolase reaction of the S-1
RT subunit of pertussis toxin.";
RL J. Biol. Chem. 264:17322-17328(1989).
RN [13]
RP CHARACTERIZATION.
RX PubMed=1997420; DOI=10.1128/iai.59.3.1177-1179.1991;
RA Pizza M., Bugnoli M., Puccini P., Siciliano R., Marino G., Rappuoli R.;
RT "Further analysis of the sequence of the S1 subunit of pertussis toxin.";
RL Infect. Immun. 59:1177-1179(1991).
RN [14]
RP ACTIVE SITE, CATALYTIC MECHANISM, AND MUTAGENESIS OF CYS-75 AND GLU-163.
RX PubMed=8527486; DOI=10.1016/0300-9084(96)88143-0;
RA Locht C., Antoine R.;
RT "A proposed mechanism of ADP-ribosylation catalyzed by the pertussis toxin
RT S1 subunit.";
RL Biochimie 77:333-340(1995).
RN [15]
RP REGULATION BY BVGA.
RC STRAIN=Tohama I / ATCC BAA-589 / NCTC 13251;
RX PubMed=7592424; DOI=10.1128/jb.177.22.6486-6491.1995;
RA Boucher P.E., Stibitz S.;
RT "Synergistic binding of RNA polymerase and BvgA phosphate to the pertussis
RT toxin promoter of Bordetella pertussis.";
RL J. Bacteriol. 177:6486-6491(1995).
RN [16]
RP MUTAGENESIS OF SER-88; SER-89; SER-90 AND ARG-91.
RC STRAIN=Tohama I / BP338;
RX PubMed=10678938; DOI=10.1128/iai.68.3.1276-1281.2000;
RA Craig-Mylius K.A., Stenson T.H., Weiss A.A.;
RT "Mutations in the S1 subunit of pertussis toxin that affect secretion.";
RL Infect. Immun. 68:1276-1281(2000).
RN [17]
RP SUBCELLULAR LOCATION, TOXIN ASSEMBLY AND SECRETION, AND MUTAGENESIS OF
RP PHE-269.
RC STRAIN=Tohama I / ATCC BAA-589 / NCTC 13251;
RX PubMed=11854200; DOI=10.1128/iai.70.3.1193-1201.2002;
RA Farizo K.M., Fiddner S., Cheung A.M., Burns D.L.;
RT "Membrane localization of the S1 subunit of pertussis toxin in Bordetella
RT pertussis and implications for pertussis toxin secretion.";
RL Infect. Immun. 70:1193-1201(2002).
RN [18]
RP PERIPLASMIC TOXIN ASSEMBLY.
RC STRAIN=Tohama I / BP338;
RX PubMed=11953363; DOI=10.1128/iai.70.5.2297-2303.2002;
RA Stenson T.H., Weiss A.A.;
RT "DsbA and DsbC are required for secretion of pertussis toxin by Bordetella
RT pertussis.";
RL Infect. Immun. 70:2297-2303(2002).
RN [19]
RP TOXIN ASSEMBLY AND SECRETION.
RC STRAIN=Tohama I / BP338;
RX PubMed=14679223; DOI=10.1128/jb.186.1.43-50.2004;
RA Rambow-Larsen A.A., Weiss A.A.;
RT "Temporal expression of pertussis toxin and Ptl secretion proteins by
RT Bordetella pertussis.";
RL J. Bacteriol. 186:43-50(2004).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
RC STRAIN=10536;
RX PubMed=8075982; DOI=10.1016/s0969-2126(00)00007-1;
RA Stein P.E., Boodhoo A., Armstrong G.D., Cockle S.A., Klein M.H., Read R.J.;
RT "The crystal structure of pertussis toxin.";
RL Structure 2:45-57(1994).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH ATP.
RX PubMed=8637000; DOI=10.1006/jmbi.1996.0277;
RA Hazes B., Boodhoo A., Cockle S.A., Read R.J.;
RT "Crystal structure of the pertussis toxin-ATP complex: a molecular
RT sensor.";
RL J. Mol. Biol. 258:661-671(1996).
CC -!- FUNCTION: S1 is an NAD-dependent ADP-ribosyltransferase, which plays a
CC crucial role in the pathogenesis of B.pertussis causing disruption of
CC normal host cellular regulation. It catalyzes the ADP-ribosylation of a
CC cysteine in the alpha subunit of host heterotrimeric G proteins. In the
CC absence of G proteins it also catalyzes the cleavage of NAD(+) into
CC ADP-ribose and nicotinamide. It irreversibly uncouples the G-alpha GTP-
CC binding proteins from their membrane receptors.
CC -!- SUBUNIT: Pertussis toxin contains five different chains, S1-S5. They
CC are organized into 2 functional subunits: A, composed of S1 (which is
CC toxic) and B, containing S2, S3, S5, and two copies of S4 (B binds to
CC the membrane receptors). Dimers of S2-S4 and S3-S4 are held together by
CC S5. {ECO:0000269|PubMed:8637000}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11854200}. Note=The
CC individual chains are secreted by a sec-dependent mechanism into the
CC periplasm. Then, S1 associates with the outer membrane before it joins
CC with the B subunit to form the secretion-competent holotoxin. The type
CC IV secretion system ptl mediates secretion of assembled toxin through
CC the outer membrane.
CC -!- INDUCTION: Activated by the two-component regulatory system BvgS/BvgA.
CC -!- DOMAIN: The region which spans amino acids 42-49 is required for
CC enzymatic activity and contributes to the formation of a potentially
CC important antigenic determinant. {ECO:0000269|PubMed:2455296}.
CC -!- PHARMACEUTICAL: Currently used in vaccines available under the names
CC Daptacel (Sanofi Pasteur), Infanrix (GlaxoSmithKline), Pediarix
CC (GlaxoSmithKline), TriHIBit (Sanofi Pasteur) and Tripedia (Sanofi
CC Pasteur).
CC -!- MISCELLANEOUS: Thiol:disulfide oxidoreductases DsbA and DsbB are
CC required for periplasmic toxin assembly, whereas DbsC is important for
CC extracellular toxin secretion.
CC -!- MISCELLANEOUS: Experiments with temporal expression of PTX indicate
CC that holotoxin secretion is at a rate of 3 molecules/min/cell. Also,
CC more of toxin chains S1, S2 and S3 are produced than secreted; one half
CC of each chain is incorporated into holotoxin.
CC -!- SIMILARITY: Belongs to the bacterial exotoxin subunit A family.
CC {ECO:0000305}.
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DR EMBL; M14378; AAA83980.1; -; Genomic_DNA.
DR EMBL; M13223; AAA22981.1; -; Genomic_DNA.
DR EMBL; X16347; CAA34397.1; -; Genomic_DNA.
DR EMBL; AJ245366; CAB51472.1; -; Genomic_DNA.
DR EMBL; AJ245367; CAB51542.1; -; Genomic_DNA.
DR EMBL; AJ245368; CAB51543.1; -; Genomic_DNA.
DR EMBL; AJ506996; CAD44970.1; -; Genomic_DNA.
DR EMBL; AJ006151; CAA06893.1; -; Genomic_DNA.
DR EMBL; AJ006153; CAA06895.1; -; Genomic_DNA.
DR EMBL; AJ006155; CAA06897.1; -; Genomic_DNA.
DR EMBL; AJ006157; CAA06899.1; -; Genomic_DNA.
DR EMBL; AJ006159; CAA06901.1; -; Genomic_DNA.
DR EMBL; AJ007363; CAA07478.1; -; Genomic_DNA.
DR EMBL; AJ007364; CAA07479.1; -; Genomic_DNA.
DR EMBL; AJ506994; CAD44968.1; -; Genomic_DNA.
DR EMBL; AJ506995; CAD44969.1; -; Genomic_DNA.
DR EMBL; AY879289; AAW72734.1; -; Genomic_DNA.
DR EMBL; AJ920066; CAI72620.1; -; Genomic_DNA.
DR EMBL; BX640422; CAE44038.1; -; Genomic_DNA.
DR PIR; A24144; WEBR1P.
DR PIR; A24394; WEBR11.
DR RefSeq; NP_882282.1; NC_002929.2.
DR RefSeq; WP_010931648.1; NZ_CP039022.1.
DR PDB; 1BCP; X-ray; 2.70 A; A/G=35-269.
DR PDB; 1PRT; X-ray; 2.90 A; A/G=36-269.
DR PDB; 1PTO; X-ray; 3.50 A; A/G=26-269.
DR PDB; 6RO0; X-ray; 2.13 A; A/G=1-269.
DR PDB; 7SKI; X-ray; 1.10 A; A/B=36-214.
DR PDB; 7SKK; X-ray; 1.65 A; A/B/C/D=36-216.
DR PDB; 7SKY; X-ray; 1.37 A; A/B/C/D=36-216.
DR PDB; 7SNE; X-ray; 1.00 A; A/B/C/D=36-216.
DR PDB; 7U6Z; X-ray; 1.30 A; A/B=36-216.
DR PDBsum; 1BCP; -.
DR PDBsum; 1PRT; -.
DR PDBsum; 1PTO; -.
DR PDBsum; 6RO0; -.
DR PDBsum; 7SKI; -.
DR PDBsum; 7SKK; -.
DR PDBsum; 7SKY; -.
DR PDBsum; 7SNE; -.
DR PDBsum; 7U6Z; -.
DR AlphaFoldDB; P04977; -.
DR SMR; P04977; -.
DR STRING; 257313.BP3783; -.
DR TCDB; 1.C.72.1.1; the pertussis toxin (ptx) family.
DR GeneID; 45390929; -.
DR KEGG; bpe:BP3783; -.
DR PATRIC; fig|257313.5.peg.4087; -.
DR eggNOG; ENOG50339NB; Bacteria.
DR HOGENOM; CLU_1081641_0_0_4; -.
DR OMA; YIYQIRA; -.
DR BRENDA; 2.4.2.30; 899.
DR EvolutionaryTrace; P04977; -.
DR Proteomes; UP000002676; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR003898; Borpert_toxA.
DR Pfam; PF02917; Pertussis_S1; 1.
DR PRINTS; PR01395; BORPETOXINA.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Glycosyltransferase; NAD; Nucleotidyltransferase; Pharmaceutical;
KW Reference proteome; Secreted; Signal; Toxin; Transferase; Virulence;
KW Whooping cough.
FT SIGNAL 1..34
FT CHAIN 35..269
FT /note="Pertussis toxin subunit 1"
FT /id="PRO_0000019359"
FT ACT_SITE 69
FT ACT_SITE 163
FT BINDING 60
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT DISULFID 75..235
FT VARIANT 68
FT /note="D -> E (in strain: 10536, CZ, 18323 and B6)"
FT VARIANT 129
FT /note="N -> S (in strain: CS)"
FT VARIANT 196
FT /note="S -> P (in strain: CZ and 18323)"
FT VARIANT 228
FT /note="M -> I (in strain: 287, Al1561, B572, CHANG and
FT HAV)"
FT VARIANT 232
FT /note="I -> M (in strain: CZ and 18323)"
FT VARIANT 232
FT /note="I -> V (in strain: 10536 and B6)"
FT MUTAGEN 75
FT /note="C->G: 38% of wild-type NAD-glycohydrolase activity."
FT /evidence="ECO:0000269|PubMed:8527486"
FT MUTAGEN 75
FT /note="C->S: 33% of wild-type NAD-glycohydrolase activity."
FT /evidence="ECO:0000269|PubMed:8527486"
FT MUTAGEN 75
FT /note="Missing: More than 100-fold reduction of NAD-
FT glycohydrolase activity."
FT /evidence="ECO:0000269|PubMed:8527486"
FT MUTAGEN 88
FT /note="S->G: No functional toxin produced although some
FT mature size S1 protein accumulates in the periplasm."
FT /evidence="ECO:0000269|PubMed:10678938"
FT MUTAGEN 89
FT /note="S->G: Very low amount of final toxin secreted;
FT approximately 50% of wild-type toxin level accumulate in
FT the periplasm despite near wild-type levels of mature size
FT S1 in the periplasm."
FT /evidence="ECO:0000269|PubMed:10678938"
FT MUTAGEN 90
FT /note="S->G: Very low amount of final toxin secreted;
FT approximately 50% of wild-type toxin level accumulate in
FT the periplasm despite near wild-type levels of mature size
FT S1 in the periplasm."
FT /evidence="ECO:0000269|PubMed:10678938"
FT MUTAGEN 91
FT /note="R->K: Very low amounts of final toxin secreted;
FT about 60% of wild-type toxin levels accumulate in the
FT periplasm. Near wild-type levels of mature size S1 in the
FT periplasm."
FT /evidence="ECO:0000269|PubMed:10678938"
FT MUTAGEN 163
FT /note="E->D: Reduction of several orders of magnitude of
FT enzymatic activity."
FT /evidence="ECO:0000269|PubMed:8527486"
FT MUTAGEN 163
FT /note="Missing: Dramatic decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:8527486"
FT MUTAGEN 269
FT /note="Missing: Affects both protein stability and outer
FT membrane targeting."
FT /evidence="ECO:0000269|PubMed:11854200"
FT STRAND 39..47
FT /evidence="ECO:0007829|PDB:6RO0"
FT HELIX 49..55
FT /evidence="ECO:0007829|PDB:6RO0"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:6RO0"
FT HELIX 66..70
FT /evidence="ECO:0007829|PDB:6RO0"
FT TURN 71..74
FT /evidence="ECO:0007829|PDB:6RO0"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:1BCP"
FT STRAND 82..89
FT /evidence="ECO:0007829|PDB:6RO0"
FT HELIX 91..110
FT /evidence="ECO:0007829|PDB:6RO0"
FT STRAND 118..126
FT /evidence="ECO:0007829|PDB:6RO0"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:6RO0"
FT HELIX 134..145
FT /evidence="ECO:0007829|PDB:6RO0"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:6RO0"
FT HELIX 152..160
FT /evidence="ECO:0007829|PDB:6RO0"
FT STRAND 163..170
FT /evidence="ECO:0007829|PDB:6RO0"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:6RO0"
FT STRAND 175..184
FT /evidence="ECO:0007829|PDB:6RO0"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:6RO0"
FT STRAND 189..196
FT /evidence="ECO:0007829|PDB:6RO0"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:6RO0"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:6RO0"
FT TURN 228..231
FT /evidence="ECO:0007829|PDB:6RO0"
FT HELIX 234..240
FT /evidence="ECO:0007829|PDB:6RO0"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:6RO0"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:6RO0"
SQ SEQUENCE 269 AA; 29974 MW; F6C88C16DA6B08AB CRC64;
MRCTRAIRQT ARTGWLTWLA ILAVTAPVTS PAWADDPPAT VYRYDSRPPE DVFQNGFTAW
GNNDNVLDHL TGRSCQVGSS NSAFVSTSSS RRYTEVYLEH RMQEAVEAER AGRGTGHFIG
YIYEVRADNN FYGAASSYFE YVDTYGDNAG RILAGALATY QSEYLAHRRI PPENIRRVTR
VYHNGITGET TTTEYSNARY VSQQTRANPN PYTSRRSVAS IVGTLVRMAP VIGACMARQA
ESSEAMAAWS ERAGEAMVLV YYESIAYSF
