T3DB: alpha-Amanitin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (14)XML

Targets (14)

Record Information

Version

2.0

Creation Date

2009-07-03 17:43:41 UTC

Update Date

2014-12-24 20:25:31 UTC

Accession Number

T3D2450

Identification

Common Name

alpha-Amanitin

Class

Small Molecule

Description

alpha-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

MOL SDF PDB SMILES InChI

Synonyms

Synonym
.alpha.-amanitin
a-Amanitin
Alpha-amanitin
Alpha-amanitin, amanita SP.
Alpha-amanitine
Alpha-amatoxin
Amanitin
α-Amanitin

Chemical Formula

C₃₉H₅₄N₁₀O₁₄S

Average Molecular Mass

918.970 g/mol

Monoisotopic Mass

918.354 g/mol

CAS Registry Number

23109-05-9

IUPAC Name

2-[(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 Name

2-[(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

SMILES

CCC(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 Identifier

InChI=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 Key

InChIKey=CIORWBWIBBPXCG-NUCBJAHASA-N

Chemical Taxonomy

Description

belongs to the class of inorganic compounds known as alkaline earth metal bromides. These are inorganic compounds in which the largest halogen atom is Bromine, and the heaviest metal atom a lanthanide.

Kingdom

Inorganic compounds

Super Class

Mixed metal/non-metal compounds

Class

Alkaline earth metal salts

Sub Class

Alkaline earth metal bromides

Direct Parent

Alkaline earth metal bromides

Alternative Parents

Inorganic salts

Substituents

Alkaline earth metal bromide
Inorganic salt

Molecular Framework

Not Available

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Not Available

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Chemical Roles

EC 2.7.7.6 (RNA polymerase) inhibitor

Physical Properties

State

Liquid

Appearance

Clear solution.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	>10 mg/mL
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	7.41 g/L	ALOGPS
logP	-1.6	ALOGPS
logP	-7.7	ChemAxon
logS	-2.1	ALOGPS
pKa (Strongest Acidic)	9.38	ChemAxon
pKa (Strongest Basic)	-5.5	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	14	ChemAxon
Hydrogen Donor Count	13	ChemAxon
Polar Surface Area	380.88 Å²	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	221.31 m³·mol⁻¹	ChemAxon
Polarizability	89.27 Å³	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0ue9-0000000059-5d330e162e89226a9343	2019-02-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-001i-0000000093-0780aade1e4ae67e31d9	2019-02-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001i-0000000090-69ea453200cbc05490e4	2019-02-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-014j-0000000096-0573e1030ee2e76d7426	2019-02-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01r7-3000000190-70524d0eb275d9469439	2019-02-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000020-78993b435a02d829e2b4	2019-02-23	View Spectrum

Toxicity Profile

Route of Exposure

Oral, dermal, inhalation, and parenteral (contaminated drugs). (2)

Mechanism of Toxicity

Amanitin 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)

Metabolism

Free 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 Values

LD50: 0.1 mg/kg (Oral, Mouse) (3)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

It 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 Level

Not Available

Health Effects

Around 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)

Symptoms

Few 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)

Treatment

Treatment 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

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

2100

ChEMBL ID

Not Available

ChemSpider ID

Not Available

KEGG ID

C08438

UniProt ID

A8W7M4

OMIM ID

ChEBI ID

37415

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

alpha-Amanitin

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Alpha-amanitin

References

Synthesis Reference

Not Available

MSDS

T3D2450.pdf

General References

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 ]
Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
Wikipedia. alpha-Amanitin. Last Updated 25 May 2009. [Link]
Wikipedia. Amatoxin. Last Updated 31 July 2009. [Link]
Wikipedia. Mushroom poisoning. Last Updated 10 August 2009. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. DNA-directed RNA polymerase II subunit RPB1

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

Target Details

2. DNA-directed RNA polymerase II subunit RPB11-a

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

Target Details

3. DNA-directed RNA polymerase II subunit RPB11-b1

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

Target Details

4. DNA-directed RNA polymerase II subunit RPB11-b2

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

Target Details

5. DNA-directed RNA polymerase II subunit RPB2

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

Target Details

6. DNA-directed RNA polymerase II subunit RPB3

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

Target Details

7. DNA-directed RNA polymerase II subunit RPB4

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

Target Details

8. DNA-directed RNA polymerase II subunit RPB7

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

Target Details

9. DNA-directed RNA polymerase II subunit RPB9

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

Target Details

10. DNA-directed RNA polymerases I, II, and III subunit RPABC1

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

Target Details

11. DNA-directed RNA polymerases I, II, and III subunit RPABC2

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

Target Details

12. DNA-directed RNA polymerases I, II, and III subunit RPABC3

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

Target Details

13. DNA-directed RNA polymerases I, II, and III subunit RPABC4

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

Target Details

14. DNA-directed RNA polymerases I, II, and III subunit RPABC5

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

alpha-Amanitin (T3D2450)

Structure for T3D2450: alpha-Amanitin

Targets

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