Dermonecrotic toxin (Pasteurella multocida) (T3D2606)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (5)XML
Targets (5)
Record Information
Version2.0
Creation Date2009-07-06 18:11:29 UTC
Update Date2014-12-24 20:25:46 UTC
Accession NumberT3D2606
Identification
Common NameDermonecrotic toxin (Pasteurella multocida)
ClassProtein
DescriptionPasteurella multocida toxin (PMT) is the major pathogenic deteriment of Pasteurella multocida. Pasteurella multocida can cause a zoonotic infection in humans, which typically is a result of bites or scratches from domestic pets. (2)
Compound Type
  • Amide
  • Amine
  • Bacterial Toxin
  • Natural Compound
  • Organic Compound
  • Protein
Protein StructureT3d2606
Synonyms
Synonym
Dermonecrotic toxin
DNT
Mitogenic toxin
PMT
Chemical FormulaNot Available
Average Molecular Mass146382.000 g/mol
CAS Registry NumberNot Available
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 (3) ; inhalation (3) ; dermal (3)
Mechanism of ToxicityStimulation of several signalling pathways is induced by PMT. Most remarkable is a potent mitogenic effect. Phospholipase C-beta and the small GTPase Rho are activated due to stimulation of heterotrimeric G proteins of the Galpha(q), Galpha(i), and Galpha(12/13) families. (1)
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/SourcesPasteurella multocida toxin (PMT) is the major pathogenic deteriment of Pasteurella multocida. (2)
Minimum Risk LevelNot Available
Health EffectsPasteurella multocida toxin (PMT) is the major pathogenic deteriment of Pasteurella multocida. Pasteurella multocida can cause a zoonotic infection in humans, which typically is a result of bites or scratches from domestic pets. This causes an inflammatory reaction at the infection site (generally a diffuse localized cellulitis). It can also infect other locales, such as the respiratory tract. In more serious cases, a bacteremia can result, causing an osteomyelitis or endocarditis. The bacteria may also cross the blood-brain barrier and cause a meningitis. (2)
SymptomsPasteurella multocida can cause a zoonotic infection in humans, which causes an inflammatory reaction at the infection site (generally a diffuse localized cellulitis). It can also infect other locales, such as the respiratory tract. In more serious cases, a bacteremia can result, causing an osteomyelitis or endocarditis. The bacteria may also cross the blood-brain barrier and cause a meningitis. (2)
TreatmentThis bacterium can be effectively treated with beta-lactam antibiotics, which inhibit cell wall synthesis. It can also be treated with fluoroquinolones or tetracyclines; fluoroquinolones inhibit bacterial DNA synthesis and tetracyclines interfere with protein synthesis by binding to the bacterial 30S ribosomal subunit. Because P. multocida is most often acquired as a result of a bite (notably dog), infections are frequently polymicrobial and involve anaerobic bacteria. As a result, amoxicillin-clavulanate (a beta-lactamase inhibitor/penicillin combination) is seen as the treatment of choice. (2)
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 IDP17452
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDDermonecrotic toxin
PDB ID2EBF
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D2606.pdf
General References
  1. Orth JH, Preuss I, Fester I, Schlosser A, Wilson BA, Aktories K: Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7179-84. doi: 10.1073/pnas.0900160106. Epub 2009 Apr 15. [19369209 ]
  2. Wikipedia. Pasteurella multocida. Last Updated 5 August 2009. [Link]
  3. Wikipedia. Bacterial toxin. Last Updated 27 February 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Guanine nucleotide-binding protein G(i) subunit alpha-1
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. Orth JH, Preuss I, Fester I, Schlosser A, Wilson BA, Aktories K: Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7179-84. doi: 10.1073/pnas.0900160106. Epub 2009 Apr 15. [19369209 ]
Target Details
2. Guanine nucleotide-binding protein G(i) subunit alpha-2
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. Orth JH, Preuss I, Fester I, Schlosser A, Wilson BA, Aktories K: Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7179-84. doi: 10.1073/pnas.0900160106. Epub 2009 Apr 15. [19369209 ]
Target Details
3. Guanine nucleotide-binding protein G(q) subunit alpha
General Function:
Type 2a serotonin receptor binding
Specific Function:
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro) (By similarity).
Gene Name:
GNAQ
Uniprot ID:
P50148
Molecular Weight:
42141.67 Da
References
  1. Orth JH, Preuss I, Fester I, Schlosser A, Wilson BA, Aktories K: Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7179-84. doi: 10.1073/pnas.0900160106. Epub 2009 Apr 15. [19369209 ]
Target Details
4. Guanine nucleotide-binding protein subunit alpha-12
General Function:
Signal transducer activity
Specific Function:
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. May play a role in the control of cell migration through the TOR signaling cascade.
Gene Name:
GNA12
Uniprot ID:
Q03113
Molecular Weight:
44278.81 Da
References
  1. Orth JH, Preuss I, Fester I, Schlosser A, Wilson BA, Aktories K: Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7179-84. doi: 10.1073/pnas.0900160106. Epub 2009 Apr 15. [19369209 ]
Target Details
5. Guanine nucleotide-binding protein subunit alpha-13
General Function:
Type 1 angiotensin receptor binding
Specific Function:
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
Gene Name:
GNA13
Uniprot ID:
Q14344
Molecular Weight:
44049.2 Da
References
  1. Orth JH, Preuss I, Fester I, Schlosser A, Wilson BA, Aktories K: Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7179-84. doi: 10.1073/pnas.0900160106. Epub 2009 Apr 15. [19369209 ]