Record Information
Version2.0
Creation Date2009-07-06 18:11:35 UTC
Update Date2014-12-24 20:25:46 UTC
Accession NumberT3D2620
Identification
Common NamePneumolysin
ClassProtein
DescriptionPneumolysin (PLY) is the cytolysin produced by Streptococcus pneumoniae and is a key virulence factor. The protein contains 471 amino acids and four structural domains. Pneumolysin belongs to a family of protein toxins known as the 'thiol-activated cytolysins'. It is a member of a large family of highly conserved, cholesterol binding toxins. The cholesterol-dependent cytolysins are pore-forming toxins. (3)
Compound Type
  • Amide
  • Amine
  • Bacterial Toxin
  • Natural Compound
  • Organic Compound
  • Protein
Protein StructureT3d2620
Synonyms
Synonym
Ply
Thiol-activated cytolysn
Chemical FormulaNot Available
Average Molecular Mass52898.050 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 (4) ; inhalation (4) ; dermal (4)
Mechanism of ToxicityPneumolysin binds to cholesterol the undergoes oligomerization and membrane pore formation. Pneumolysin also activates the classical pathway of complement. Mutational analysis of the toxin and knowledge of sequence variation in outbreak strains suggests that additional activities of biologic importance exist. Pneumolysin activates a large number of genes, some by epigenetic modification, in eukaryotic cells and multiple signal transduction pathways. Cytolytic effects contribute to lung injury and neuronal damage while proinflammatory effects compound tissue damage. (2, 3)
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 ValuesLD50: 1.5 ug/mg (Intravenous, Rabbit) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesPneumolysin (PLY) is the cytolysin produced by Streptococcus pneumoniae and is a key virulence factor. (3)
Minimum Risk LevelNot Available
Health EffectsPneumolysin is hemolytic and cytolytic. Cytolytic effects contribute to lung injury and neuronal damage while proinflammatory effects compound tissue damage. Streptococcus pneumoniae causes many types of pneumococcal infection, including pneumonia, acute sinusitis, otitis media, meningitis, bacteremia, sepsis, osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, cellulitis, and brain abscess.(2, 3)
SymptomsPneumolysin is hemolytic and cytolytic. Cytolytic effects contribute to lung injury and neuronal damage while proinflammatory effects compound tissue damage. (2, 3)
TreatmentS. pneumoniae used to be treated with penicillin, but there has been an increasing prevalence of penicillin resistance. A varying proportion of strains may also be resistant to cephalosporins, macrolides (such as erythromycin), tetracycline, clindamycin and the quinolones. Most isolates remain susceptible to vancomycin, and advanced beta-lactam antibiotics (cephalosporins) are commonly used in combination with other drugs to treat meningitis and community-acquired pneumonia. In adults, recently developed fluoroquinolones such as levofloxacin and moxifloxacin are often used to provide empiric coverage for patients with pneumonia. (3)
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 IDP0C2J9
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPneumolysin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkPneumolysin
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Gill DM: Bacterial toxins: a table of lethal amounts. Microbiol Rev. 1982 Mar;46(1):86-94. [6806598 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Pneumococcal infection. Last Updated 14 May 2009. [Link]
  4. Wikipedia. Bacterial toxin. Last Updated 27 February 2009. [Link]
  5. Wikipedia. Streptococcus pneumoniae. Last Updated 7 August 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
  2. The UniProt Consortium. The Universal Protein Resource (UniProt) Nucleic Acids Res. 2008;36:D190-D195.
  3. Wikipedia. Pneumococcal infection. Last Updated 14 May 2009. [Link]