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Record Information
Version2.0
Creation Date2009-07-06 18:11:24 UTC
Update Date2014-12-24 20:25:45 UTC
Accession NumberT3D2595
Identification
Common NamePertussis toxin
ClassProtein
DescriptionPertussis toxin (PTX; 106 kDa) is one of the numerous toxins from Bordetella pertussis, the agent of the whooping cough disease. Pertussis toxin belongs to the A-B5 bacterial toxin superfamily. It is composed of a B oligomer (subunits S1, S2, S3, (2)S4, and S5), responsible for its binding to target cells, and a A moiety (subunit S1) that exhibits ADP-ribosyltransferase activity. (1, 4)
Compound Type
  • Amide
  • Amine
  • Bacterial Toxin
  • Natural Compound
  • Organic Compound
  • Protein
Protein StructureT3d2595
Synonyms
Synonym
Pertussis toxin subunit 1
Pertussis toxin subunit 2
Pertussis toxin subunit 3
Pertussis toxin subunit 4
Pertussis toxin subunit 5
ptxA
ptxB
ptxC
ptxD
ptxE
Chemical FormulaNot Available
Average Molecular Mass29973.970 g/mol
CAS Registry Number70323-44-3
SequenceNot Available
Chemical Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceClear solution.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility>10 mg/mL
LogPNot Available
Predicted PropertiesNot Available
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Toxicity Profile
Route of ExposureIngestion (7) ; inhalation (7) ; dermal (7)
Mechanism of ToxicityAfter binding to the cell receptors, pertussis toxin (PTX) is endocytosed and the A moiety translocates into the cytosol where it expresses the ADP-ribosyltransferase activity on heterotrimeric G proteins. ADP-ribosylated G-proteins loose their ability to transduce signals. Furthermore, the binding of the B oligomer to the cell receptor is able to trigger different signal transduction pathways which, in turn, can lead to DNA synthesis in B cells, proliferation in T lymphocytes, and others. (1, 4)
MetabolismFree toxin may be removed by opsonization via the reticuloendothelial system (primarily the liver and kidneys) or it may be degraded through cellular internalization via the lysosomes. Lysosomes are membrane-enclosed organelles that contain an array of digestive enzymes, including several proteases.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesPertussis toxin (PTX; 106 kDa) is one of the numerous toxins from Bordetella pertussis, the agent of the whooping cough disease. (1, 4)
Minimum Risk LevelNot Available
Health EffectsPertussis toxin is an exotoxin produced by Bordetella pertussis, the agent of the whooping cough disease. (4, 3, 2)
SymptomsAfter an incubation period that is typically seven to ten days, pertussis in infants and young children is characterized initially by mild respiratory infection symptoms such as mild coughing, sneezing, and runny nose (catarrhal stage). After one to two weeks, the coughing develops into uncontrollable fits, each with five to ten forceful coughs, followed by a high-pitched "whoop" sound as the patient struggles to breathe in afterwards (paroxysmal stage). Coughing fits are commonly followed by vomiting, and can lead to malnutrition. Fits can occur on their own or can be triggered by eating; they usually occur in groups, with multiple episodes every hour around the clock. This stage lasts two to eight weeks, and sometimes longer. A gradual transition then occurs to the convalescent stage, which usually lasts one to two weeks. Common complications of the disease include pneumonia, encephalopathy, earache, and seizures. Infection in newborns is particularly severe, with a death risk of up to 3%, often caused by severe pulmonary hypertension. (6)
TreatmentTreatment with an effective antibiotic (erythromycin or azithromycin) shortens the infectious period but does not generally alter the outcome of the disease; however, when treatment is initiated during the catarrhal stage, symptoms may be less severe. Three macrolides (erythromycin, azithromycin and clarithromycin) are used in the U.S. for treatment of pertussis; trimethoprim-sulfamethoxazole is generally used when a macrolide is ineffective or is contraindicated. (6)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound IDNot Available
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDP04977
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPertussis toxin
PDB ID1BCP
ACToR IDNot Available
Wikipedia LinkPertussis_toxin
References
Synthesis ReferenceNot Available
MSDST3D2595.pdf
General References
  1. Fabbri A, Travaglione S, Falzano L, Fiorentini C: Bacterial protein toxins: current and potential clinical use. Curr Med Chem. 2008;15(11):1116-25. [18473807 ]
  2. Ladant D, Ullmann A: Bordatella pertussis adenylate cyclase: a toxin with multiple talents. Trends Microbiol. 1999 Apr;7(4):172-6. [10217833 ]
  3. Locht C, Antoine R, Jacob-Dubuisson F: Bordetella pertussis, molecular pathogenesis under multiple aspects. Curr Opin Microbiol. 2001 Feb;4(1):82-9. [11173039 ]
  4. Smith AM, Guzman CA, Walker MJ: The virulence factors of Bordetella pertussis: a matter of control. FEMS Microbiol Rev. 2001 May;25(3):309-33. [11348687 ]
  5. Wikipedia. Pertussis toxin. Last Updated 9 August 2009. [Link]
  6. Wikipedia. Whooping Cough. Last Updated 7 August 2009. [Link]
  7. Wikipedia. Bacterial toxin. Last Updated 27 February 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Signal transducer activity
Specific Function:
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.
Gene Name:
GNAI1
Uniprot ID:
P63096
Molecular Weight:
40360.685 Da
References
  1. Wikipedia. Pertussis toxin. Last Updated 9 August 2009. [Link]
General Function:
Signal transducer activity
Specific Function:
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division.Isoform sGi2: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool.
Gene Name:
GNAI2
Uniprot ID:
P04899
Molecular Weight:
40450.51 Da
References
  1. Wikipedia. Pertussis toxin. Last Updated 9 August 2009. [Link]
General Function:
Signal transducer activity
Specific Function:
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(o) protein function is not clear. Stimulated by RGS14.
Gene Name:
GNAO1
Uniprot ID:
P09471
Molecular Weight:
40050.165 Da
References
  1. Wikipedia. Pertussis toxin. Last Updated 9 August 2009. [Link]
General Function:
Signal transducer activity
Specific Function:
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Transducin is an amplifier and one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase.
Gene Name:
GNAT1
Uniprot ID:
P11488
Molecular Weight:
40040.415 Da
References
  1. Wikipedia. Pertussis toxin. Last Updated 9 August 2009. [Link]
General Function:
Metal ion binding
Specific Function:
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Transducin is an amplifier and one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase.
Gene Name:
GNAT2
Uniprot ID:
P19087
Molecular Weight:
40175.435 Da
References
  1. Wikipedia. Pertussis toxin. Last Updated 9 August 2009. [Link]
General Function:
Metal ion binding
Specific Function:
Guanine nucleotide-binding protein (G protein) alpha subunit playing a prominent role in bitter and sweet taste transduction as well as in umami (monosodium glutamate, monopotassium glutamate, and inosine monophosphate) taste transduction. Transduction by this alpha subunit involves coupling of specific cell-surface receptors with a cGMP-phosphodiesterase; Activation of phosphodiesterase lowers intracellular levels of cAMP and cGMP which may open a cyclic nucleotide-suppressible cation channel leading to influx of calcium, ultimately leading to release of neurotransmitter. Indeed, denatonium and strychnine induce transient reduction in cAMP and cGMP in taste tissue, whereas this decrease is inhibited by GNAT3 antibody. Gustducin heterotrimer transduces response to bitter and sweet compounds via regulation of phosphodiesterase for alpha subunit, as well as via activation of phospholipase C for beta and gamma subunits, with ultimate increase inositol trisphosphate and increase of intracellular Calcium. GNAT3 can functionally couple to taste receptors to transmit intracellular signal: receptor heterodimer TAS1R2/TAS1R3 senses sweetness and TAS1R1/TAS1R3 transduces umami taste, whereas the T2R family GPCRs act as bitter sensors. Functions also as lumenal sugar sensors in the gut to control the expression of the Na+-glucose transporter SGLT1 in response to dietaty sugar, as well as the secretion of Glucagon-like peptide-1, GLP-1 and glucose-dependent insulinotropic polypeptide, GIP. Thus, may modulate the gut capacity to absorb sugars, with implications in malabsorption syndromes and diet-related disorders including diabetes and obesity.
Gene Name:
GNAT3
Uniprot ID:
A8MTJ3
Molecular Weight:
40356.655 Da
References
  1. Wikipedia. Pertussis toxin. Last Updated 9 August 2009. [Link]