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Record Information
Version2.0
Creation Date2009-07-03 17:43:41 UTC
Update Date2014-12-24 20:25:31 UTC
Accession NumberT3D2450
Identification
Common Namealpha-Amanitin
ClassSmall Molecule
Descriptionalpha-Amanitin or α-amanitin is a cyclic peptide of eight amino acids. It is possibly the most deadly of all the amatoxins, toxins found in several members of the Amanita genus of mushrooms, one being the Death cap (Amanita phalloides) as well as the Destroying angel, a complex of similar species, principally A. virosa and A. bisporigera. It is also found in the mushrooms Galerina marginata and Conocybe filaris. (3)
Compound Type
  • Amide
  • Amine
  • Fungal Toxin
  • Mycotoxin
  • Natural Compound
  • Organic Compound
  • Protein
Chemical Structure
Thumb
Synonyms
Synonym
.alpha.-amanitin
a-Amanitin
Alpha-amanitin
Alpha-amanitin, amanita SP.
Alpha-amanitine
Alpha-amatoxin
Amanitin
α-Amanitin
Chemical FormulaC39H54N10O14S
Average Molecular Mass918.970 g/mol
Monoisotopic Mass918.354 g/mol
CAS Registry Number23109-05-9
IUPAC Name2-[(1R,4S,10S,13S,16S,27R,34S)-34-(butan-2-yl)-13-[(3R)-3,4-dihydroxybutan-2-yl]-8,22-dihydroxy-2,5,11,14,27,30,33,36,39-nonaoxo-27λ⁴-thia-3,6,12,15,25,29,32,35,38-nonaazapentacyclo[14.12.11.0⁶,¹⁰.0¹⁸,²⁶.0¹⁹,²⁴]nonatriaconta-18(26),19,21,23-tetraen-4-yl]acetamide
Traditional Name2-[(1R,4S,10S,13S,16S,27R,34S)-13-[(3R)-3,4-dihydroxybutan-2-yl]-8,22-dihydroxy-2,5,11,14,27,30,33,36,39-nonaoxo-34-(sec-butyl)-27λ⁴-thia-3,6,12,15,25,29,32,35,38-nonaazapentacyclo[14.12.11.0⁶,¹⁰.0¹⁸,²⁶.0¹⁹,²⁴]nonatriaconta-18(26),19,21,23-tetraen-4-yl]acetamide
SMILESCCC(C)[C@@H]1NC(=O)CNC(=O)[C@@H]2CC3=C(NC4=CC(O)=CC=C34)[S@](=O)C[C@H](NC(=O)CNC1=O)C(=O)N[C@@H](CC(N)=O)C(=O)N1CC(O)C[C@H]1C(=O)N[C@@H](C(C)[C@@H](O)CO)C(=O)N2
InChI IdentifierInChI=1S/C39H54N10O14S/c1-4-16(2)31-36(60)42-11-29(55)43-25-15-64(63)38-21(20-6-5-18(51)7-22(20)46-38)9-23(33(57)41-12-30(56)47-31)44-37(61)32(17(3)27(53)14-50)48-35(59)26-8-19(52)13-49(26)39(62)24(10-28(40)54)45-34(25)58/h5-7,16-17,19,23-27,31-32,46,50-53H,4,8-15H2,1-3H3,(H2,40,54)(H,41,57)(H,42,60)(H,43,55)(H,44,61)(H,45,58)(H,47,56)(H,48,59)/t16?,17?,19?,23-,24-,25-,26-,27-,31-,32-,64+/m0/s1
InChI KeyInChIKey=CIORWBWIBBPXCG-NUCBJAHASA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as amatoxins. These are cyclic peptides containing eight amino acid residues arranged in a macrobicyclic motif.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassCarboxylic acids and derivatives
Direct ParentAmatoxins
Alternative Parents
Substituents
  • Amatoxin skeleton
  • Alpha-oligopeptide
  • Alpha-amino acid or derivatives
  • Hydroxyindole
  • 3-alkylindole
  • Indole
  • Indole or derivatives
  • 1-hydroxy-2-unsubstituted benzenoid
  • Benzenoid
  • Pyrrole
  • Pyrrolidine
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Carboxamide group
  • Lactam
  • Primary carboxylic acid amide
  • Secondary alcohol
  • Secondary carboxylic acid amide
  • Sulfoxide
  • Azacycle
  • Sulfinyl compound
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organic oxide
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Carbonyl group
  • Alcohol
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical Roles
Physical Properties
StateLiquid
AppearanceClear solution.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility>10 mg/mL
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility7.41 mg/mLALOGPS
logP-1.6ALOGPS
logP-7.7ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)9.38ChemAxon
pKa (Strongest Basic)-5.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count13ChemAxon
Polar Surface Area380.88 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity221.31 m3·mol-1ChemAxon
Polarizability89.27 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (2)
Mechanism of ToxicityAmanitin has an unusually strong and specific attraction to the enzyme RNA polymerase II. Upon ingestion, it binds to the RNA polymerase II enzyme, preventing mRNA synthesis and effectively causing cytolysis of hepatocytes (liver cells). (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: 0.1 mg/kg (Oral, Mouse) (3)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIt is found in several members of the Amanita genus of mushrooms, one being the Death cap (Amanita phalloides) as well as the Destroying angel, a complex of similar species, principally A. virosa and A. bisporigera. It is also found in the mushrooms Galerina marginata and Conocybe filaris. (3)
Minimum Risk LevelNot Available
Health EffectsAround 15% of those poisoned will die within 10 days, progressing through a comatose stage to renal failure, liver failure, hepatic coma, respiratory failure and death. Those who recover are at risk of permanent liver damage. Diagnosis is difficult, and is established by observation of the clinical symptoms as well as the presence of α-amanitin in the urine. Urine screening is generally most useful within 48 hours of ingestion. (1)
SymptomsFew effects are reported within 10 hours; it is not unusual for significant effects to take as long as 24 hours after ingestion to appear, with this delay in symptoms making α-amanitin poisoning even more difficult to diagnose and all the more dangerous. By then, it is far past the time in which stomach pumping would yield an efficient result. Diarrhea and cramps are the first symptoms, but those pass, giving a false sign of remission. Typically, on the 4th to 5th day, the toxin starts to have severe effects on the liver and kidneys, leading to total system failure in both. Death usually takes place around a week from ingestion. (3)
TreatmentTreatment is mainly supportive (gastric lavage, activated carbon, fluid resuscitation) but includes various drugs to counter the amatoxins, including intravenous penicillin and cephalosporin derivatives, and, in cases of greater ingestion, can extend to an orthotopic liver transplant. The most reliable method to treat amanitin poisoning is through having the stomach pumped immediately after ingestion; however, the onset of symptoms is generally too late for this to be an option. (1)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID2100
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDC08438
UniProt IDA8W7M4
OMIM ID
ChEBI ID37415
BioCyc IDNot Available
CTD IDNot Available
Stitch IDalpha-Amanitin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAlpha-amanitin
References
Synthesis ReferenceNot Available
MSDST3D2450.pdf
General References
  1. Hamilton B, Whittle N, Shaw G, Eaglesham G, Moore MR, Lewis RJ: Human fatality associated with Pacific ciguatoxin contaminated fish. Toxicon. 2010 Oct;56(5):668-73. doi: 10.1016/j.toxicon.2009.06.007. Epub 2009 Jun 16. [19538985 ]
  2. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  3. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
  4. Wikipedia. Amatoxin. Last Updated 31 July 2009. [Link]
  5. Wikipedia. Mushroom poisoning. Last Updated 10 August 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Ubiquitin protein ligase binding
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB1 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template. At the start of transcription, a single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol II. A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol II by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition. During transcription elongation, Pol II moves on the template as the transcript elongates. Elongation is influenced by the phosphorylation status of the C-terminal domain (CTD) of Pol II largest subunit (RPB1), which serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing. Acts as an RNA-dependent RNA polymerase when associated with small delta antigen of Hepatitis delta virus, acting both as a replicate and transcriptase for the viral RNA circular genome.
Gene Name:
POLR2A
Uniprot ID:
P24928
Molecular Weight:
217174.235 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Lrr domain binding
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft (By similarity).
Gene Name:
POLR2J
Uniprot ID:
P52435
Molecular Weight:
13293.19 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Dna-directed rna polymerase activity
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft (By similarity).
Gene Name:
POLR2J2
Uniprot ID:
Q9GZM3
Molecular Weight:
13088.14 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Dna-directed rna polymerase activity
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft (By similarity).
Gene Name:
POLR2J3
Uniprot ID:
Q9H1A7
Molecular Weight:
13092.11 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Ribonucleoside binding
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB2 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template (By similarity).
Gene Name:
POLR2B
Uniprot ID:
P30876
Molecular Weight:
133895.435 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Dna-directed rna polymerase activity
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB3 is part of the core element with the central large cleft and the clamp element that moves to open and close the cleft (By similarity).
Gene Name:
POLR2C
Uniprot ID:
P19387
Molecular Weight:
31440.86 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Translation initiation factor binding
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB4 is part of a subcomplex with RPB7 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RBP4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity).
Gene Name:
POLR2D
Uniprot ID:
O15514
Molecular Weight:
16311.105 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Translation initiation factor binding
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB7 is part of a subcomplex with RPB4 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RBP4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity). Binds RNA.
Gene Name:
POLR2G
Uniprot ID:
P62487
Molecular Weight:
19294.195 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Zinc ion binding
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB9 is part of the upper jaw surrounding the central large cleft and thought to grab the incoming DNA template (By similarity).
Gene Name:
POLR2I
Uniprot ID:
P36954
Molecular Weight:
14523.1 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Dna-directed rna polymerase activity
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2E/RPB5 is part of the lower jaw surrounding the central large cleft and thought to grab the incoming DNA template. Seems to be the major component in this process (By similarity).
Gene Name:
POLR2E
Uniprot ID:
P19388
Molecular Weight:
24551.075 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Dna-directed rna polymerase activity
Specific Function:
DNA-dependent RNA polymerases catalyze the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II, and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2F/RPB6 is part of the clamp element and together with parts of RPB1 and RPB2 forms a pocket to which the RPB4-RPB7 subcomplex binds (By similarity).
Gene Name:
POLR2F
Uniprot ID:
P61218
Molecular Weight:
14477.92 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Dna-directed rna polymerase activity
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively.
Gene Name:
POLR2H
Uniprot ID:
P52434
Molecular Weight:
17143.115 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Zinc ion binding
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively.
Gene Name:
POLR2K
Uniprot ID:
P53803
Molecular Weight:
7004.145 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
General Function:
Zinc ion binding
Specific Function:
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2L/RBP10 is part of the core element with the central large cleft (By similarity).
Gene Name:
POLR2L
Uniprot ID:
P62875
Molecular Weight:
7645.02 Da
References
  1. Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]