Peptide

CyclicPepedia Knowledge Base

Visitor
Visitor
Status Profile

Alpha-Amanitin (Amatoxin) (Gamma-Amanitin)

Basic information

CPKB ID CP03957
Source

Amanita phalloides [Division : Plants and Fungi]

Taxonomy :67723 (Fungi-Basidiomycota-Agaricales-Agaricomycetes-Amanitaceae Amanita)  

Wikipedia: Amanita phalloides

Uniprot  

Family

Msdin Fungal Toxin   Uniprot  

Function

Toxin   Uniprot  

Legend

Structure

Download structure
2D img
300x300 pixels
100x100 pixels
500x500 pixels
similarity structure
Molecular Formula

C101H162N28O32S2
Molecular Weight 840.395244372 g/mol
SMILES

RUN SEA Predictions

 CC[C@H](C)[C@@H]1NC(=O)CNC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)CNC1=O  

CyclicPepedia|Seq2Struc
InChIKey
VJAFYMSODIESLG-DIXQNSHDNA-N
2D Structure
CyclicPepedia|Seq2Struc
3D Structure (Complex)
PDB|1K83  PDB|3CQZ 

Sequence

Graph alignment
Local alignment
One-letter code

IWGIGCNP

Uniprot|P85421
IUPAC Condensed
ILE-TRP-GLY-ILE-GLY-CYS-ASN-PRO  

CyclicPepedia|PP
Amino acid chain
ILE--TRP--GLY--ILE--GLY--CYS--ASN--PRO  

CyclicPepedia|PP
Graph representation
ILE,TRP,GLY,ILE,GLY,CYS,ASN,PRO  

CyclicPepedia|PP

Chemical and Physical Properties

CyclicPepedia|PP

Structure Properties

Property Name Property Value
Exact Mass 840.395244372
Number of Rings 4.0
Complexity 0.762711864406779
XlogP3 AA -1.73119999999999
Heavy Atom Count 59.0
Hydrogen Bond Donor Count 10.0
Hydrogen Bond Acceptor Count 10.0
Rotatable Bond Count 9.0
Property Name Property Value
Formal Charge 0.0
Refractivity 218.984999999999
Rule_of_Five 0.0
Number of Atoms 59.0
Topological Polar Surface Area 282.89
Refractivity 218.984999999999
Veber Rule 0.0
Ghose Filter 0.0
Property Name Property Value
RDKit Fingerprint
11100111110100100111110011111000111000100111010000111011001001001110101101101101111111000010110011110111110101001010011001110111010001011000111000011111000110010101001010011111000111001111100100110100101001001000000110000000010100000101011110001110011101101111000110001110000110101111110000000010011011010111101011010001110100000011111111010110101100000010111101001001000011000010000000101010010100000110100100001110000010110101101000110011111011100000010100010110111000011000000000001110001011010110100100101100111100011110110010011101000110000101100011010110101000100100010110001000000110111100101110111001001010011010100000111001110100101100101110100111011001000110111110111111010111001101011100010000101101100000000111110011101101011110101010000010001110101011101110011000000111101001011010011011001000011010110000001101111010110000011011111101100001110111011100100011000110000101111000010011000101000110111101110110011110011010110001011110101000011000111001010000011001010100001001110001110101000010010000111001111101110111110110001110110001001011010101001010101001100011110001001001110110001101001101011010000001101010100110101101010011001100111000011000101110110110100111001000010011011110100011000000100001001101110110100100011101010111010010011001100111000110101110001010100001111000110101001001011110111100100111100101100001011001111111010001010110110001110010110001111101001111001010000011000001011100100011100101101011001000010011111110101001001011100110111100110101110001110000111011011010000000100100100111111001100101011000010100110111110100010111100000101100100111001011010111100010000011100111001011010010100010110110110100000000000010010010011011000011010110001011100101000000110000111110000100110101000101010111001000100000100111011001011100111010010110100000001000100001111010000011100001111011101100100111110000111110100111111010000001100001010000111011101010010100001101101110010100101101000001011001010111001110000111110110000011011001011111011000001001101001100111000101110100110110000000000001101110010100000000111101000011
Morgan Fingerprint
0100110000100000000100000000100001000000001000000000000000000000110000000000000010000000001000000000000000000100000100010000000000100000000010000001000000000000100000000000000100000000000000000000000000000000000000000000000000000101000000000000000000000000000000000000000000000000000100001000001000000100000000000010000000000101100001000000100000000000000010000000100000000000000000000000000000000000000000000000000000000000000000000001000010000010000000001010000000000000001000000010000000001000000000010001000000000001100000000000000000000000000001010000000000000000000000000000000100000000000000000000000000000000000000000000000000100000000000000010000000000000010001000000000000001000000000000000000000000000000000000000001000000000000000000000000000000011000000000000000000000000000000000000001000000011000000000000000000000000000000000010001001000001000000000000000000100000000000000000010100000000000000000100000000000010000000010000000000000000001000000000000000000000010000000000000100000010000010000000000000010000
MACCS Keys
00000000000000000000000000000000000000000000000000000110000000000100000000000001101111001011100111001100110000110011011011100101110110001110111100111111011110111111110

Sequence Properties

Property Name Property Value
Boman Index -1.08625
Instability -18.4249999999999
Charge -0.0639904165326108
Aliphatic Index 97.5

Biologic Description

Toxicity PubChem|

TOXIC DOSE: LD(50) is 0.35 mg/kg by intraperitoneal injection into mice. LD(50) is 4 mg/kg by intravenous injection into rats, and 0.1 mg/kg by intravenous injection into dogs. LD(50) is 2 ug/kg by intracerebroventricular injection into mice, and 10 ug/kg by intracerebroventricular injection into rats.

Manufacturers

Forecasting tools

Information Source

Reference

Pubmed_ID Title DOI Journal

32414842

 Discovery and mechanistic studies of cytotoxic cyclotides from the medicinal herb 10.1074/jbc.RA120.012627.

J Biol Chem

Discovery and mechanistic studies of cytotoxic cyclotides from the medicinal herb

Abstract

  • Cyclotides are plant-derived peptides characterized by an ∼30-amino acid-long cyclic backbone and a cystine knot motif. Cyclotides have diverse bioactivities, and their cytotoxicity has attracted significant attention for its potential anticancer applications. (Linn) F. Muell is a medicinal herb widely used in India as a libido enhancer, and a previous study has reported that it may contain cyclotides. In the current study, we isolated 11 novel cyclotides and 1 known cyclotide (cycloviolacin O2) from and used tandem MS to determine their amino acid sequences. We found that among these cyclotides, hyen C comprises a unique sequence in loops 1, 2, 3, 4, and 6 compared with known cyclotides. The most abundant cyclotide in this plant, hyen D, had anticancer activity comparable to that of cycloviolacin O2, one of the most cytotoxic known cyclotides. We also provide mechanistic insights into how these novel cyclotides interact with and permeabilize cell membranes. Results from surface plasmon resonance experiments revealed that hyen D, E, L, and M and cycloviolacin O2 preferentially interact with model lipid membranes that contain phospholipids with phosphatidyl-ethanolamine headgroups. The results of a lactate dehydrogenase assay indicated that exposure to these cyclotides compromises cell membrane integrity. Using live-cell imaging, we show that hyen D induces rapid membrane blebbing and cell necrosis. Cyclotide-membrane interactions correlated with the observed cytotoxicity, suggesting that membrane permeabilization and disintegration underpin cyclotide cytotoxicity. These findings broaden our knowledge on the indigenous Indian herb and have uncovered cyclotides with potential anticancer activity.