Charybdotoxin
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Basic Info
| Common Name | Charybdotoxin(F04705) |
| 2D Structure | |
| Description | Charybdotoxin is a peptide toxin produced by the Yellow scorpion (Leiurus quinquestriatus hebraeus). It is a neurotoxin that blocks calcium-activated potassium channels.This blockade causes hyperexcitability of the nervous system. It is a close homologue of agitoxin and both toxins come from Leiurus quinquestriatus hebraeus. (L1041) |
| FRCD ID | F04705 |
| CAS Number | 95751-30-7 |
| PubChem CID | 44134622 |
| Formula | C176H289N57O56S7 |
| IUPAC Name | None |
| InChI Key | BPPXMZLBVMSRDL-UHFFFAOYSA-N |
| InChI | InChI=1S/C176H289N57O56S7/c1-81(2)58-106(149(264)213-110(62-91-67-192-80-198-91)152(267)215-112(64-127(184)246)156(271)231-135(85(8)240)170(285)219-114(69-234)157(272)200-96(36-25-54-193-174(186)187)139(254)197-68-129(248)199-97(32-17-21-50-177)140(255)222-120(75-291)162(277)208-105(49-57-296-11)148(263)214-111(63-126(183)245)153(268)203-98(33-18-22-51-178)141(256)201-100(35-20-24-53-180)144(259)223-119(74-290)161(276)205-102(38-27-56-195-176(190)191)145(260)224-121(76-292)164(279)211-107(60-89-39-41-92(243)42-40-89)150(265)221-118(73-238)173(288)289)210-143(258)101(37-26-55-194-175(188)189)202-146(261)103(44-46-125(182)244)207-163(278)123(78-294)227-168(283)133(83(5)6)229-160(275)117(72-237)217-151(266)109(61-90-66-196-95-31-16-15-30-93(90)95)212-165(280)122(77-293)225-147(262)104(45-48-131(251)252)206-142(257)99(34-19-23-52-179)204-158(273)115(70-235)220-171(286)136(86(9)241)233-172(287)137(87(10)242)232-166(281)124(79-295)226-159(274)116(71-236)218-167(282)132(82(3)4)228-155(270)113(65-128(185)247)216-169(284)134(84(7)239)230-154(269)108(59-88-28-13-12-14-29-88)209-138(253)94(181)43-47-130(249)250/h12-16,28-31,39-42,66,81-87,91,94,96-124,132-137,192,196,198,234-243,290-295H,17-27,32-38,43-65,67-80,177-181H2,1-11H3,(H2,182,244)(H2,183,245)(H2,184,246)(H2,185,247)(H,197,254)(H,199,248)(H,200,272)(H,201,256)(H,202,261)(H,203,268)(H,204,273)(H,205,276)(H,206,257)(H,207,278)(H,208,277)(H,209,253)(H,210,258)(H,211,279)(H,212,280)(H,213,264)(H,214,263)(H,215,267)(H,216,284)(H,217,266)(H,218,282)(H,219,285)(H,220,286)(H,221,265)(H,222,255)(H,223,259)(H,224,260)(H,225,262)(H,226,274)(H,227,283)(H,228,270)(H,229,275)(H,230,269)(H,231,271)(H,232,281)(H,233,287)(H,249,250)(H,251,252)(H,288,289)(H4,186,187,193)(H4,188,189,194)(H4,190,191,195) |
| Canonical SMILES | CC(C)CC(C(=O)NC(CC1CNCN1)C(=O)NC(CC(=O)N)C(=O)NC(C(C)O)C(=O)NC(CO)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CCCCN)C(=O)NC(CS)C(=O)NC(CCSC)C(=O)NC(CC(=O)N)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CS)C(=O)NC(CCCNC(=N)N)C(=O)NC(CS)C(=O)NC(CC2=CC=C(C=C2)O)C(=O)NC(CO)C(=O)O)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCC(=O)N)NC(=O)C(CS)NC(=O)C(C(C)C)NC(=O)C(CO)NC(=O)C(CC3=CNC4=CC=CC=C43)NC(=O)C(CS)NC(=O)C(CCC(=O)O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(C(C)O)NC(=O)C(CS)NC(=O)C(CO)NC(=O)C(C(C)C)NC(=O)C(CC(=O)N)NC(=O)C(C(C)O)NC(=O)C(CC5=CC=CC=C5)NC(=O)C(CCC(=O)O)N |
| Isomeric SMILES | CC(C)CC(C(=O)NC(CC1CNCN1)C(=O)NC(CC(=O)N)C(=O)NC(C(C)O)C(=O)NC(CO)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CCCCN)C(=O)NC(CS)C(=O)NC(CCSC)C(=O)NC(CC(=O)N)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CS)C(=O)NC(CCCNC(=N)N)C(=O)NC(CS)C(=O)NC(CC2=CC=C(C=C2)O)C(=O)NC(CO)C(=O)O)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCC(=O)N)NC(=O)C(CS)NC(=O)C(C(C)C)NC(=O)C(CO)NC(=O)C(CC3=CNC4=CC=CC=C43)NC(=O)C(CS)NC(=O)C(CCC(=O)O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(C(C)O)NC(=O)C(CS)NC(=O)C(CO)NC(=O)C(C(C)C)NC(=O)C(CC(=O)N)NC(=O)C(C(C)O)NC(=O)C(CC5=CC=CC=C5)NC(=O)C(CCC(=O)O)N |
| Synonyms |
FT-0688988
|
| Classifies |
Animal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organic Polymers |
| Class | Polypeptides |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Polypeptides |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Polypeptide - Alpha peptide - Tyrosine or derivatives - Arginine or derivatives - Phenylalanine or derivatives - Glutamic acid or derivatives - Glutamine or derivatives - Methionine or derivatives - Asparagine or derivatives - Leucine or derivatives - N-acyl-alpha-amino acid - N-acyl-alpha amino acid or derivatives - Valine or derivatives - Alpha-amino acid amide - Triptan - Cysteine or derivatives - Serine or derivatives - Alpha-amino acid or derivatives - Amphetamine or derivatives - 3-alkylindole - N-substituted-alpha-amino acid - Indole or derivatives - Indole - Tricarboxylic acid or derivatives - Beta-hydroxy acid - Hydroxy fatty acid - Amino fatty acid - 1-hydroxy-2-unsubstituted benzenoid - Phenol - Fatty acyl - Substituted pyrrole - N-acyl-amine - Monocyclic benzene moiety - Benzenoid - Hydroxy acid - Fatty amide - Imidazolidine - Heteroaromatic compound - Pyrrole - Amino acid or derivatives - Amino acid - Carboxamide group - Guanidine - Secondary carboxylic acid amide - Secondary alcohol - Primary carboxylic acid amide - Aminal - Alkylthiol - Azacycle - Carboxylic acid derivative - Carboxylic acid - Organoheterocyclic compound - Dialkylthioether - Sulfenyl compound - Carboximidamide - Thioether - Organonitrogen compound - Organic nitrogen compound - Carbonyl group - Organooxygen compound - Hydrocarbon derivative - Primary amine - Amine - Organic oxygen compound - Primary alcohol - Alcohol - Organic oxide - Imine - Organosulfur compound - Organopnictogen compound - Primary aliphatic amine - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 4324.011 |
| Hydrogen Bond Donor Count | 76 |
| Hydrogen Bond Acceptor Count | 73 |
| Rotatable Bond Count | 149 |
| Complexity | 10000 |
| Monoisotopic Mass | 4320.956 |
| Exact Mass | 4321.96 |
| XLogP | -27.9 |
| Formal Charge | 0 |
| Heavy Atom Count | 296 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 41 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB- | 0.9686 |
| Human Intestinal Absorption | HIA+ | 0.9509 |
| Caco-2 Permeability | Caco2- | 0.7866 |
| P-glycoprotein Substrate | Substrate | 0.8958 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9063 |
| Non-inhibitor | 0.9681 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.7251 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.4367 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8027 |
| CYP450 2D6 Substrate | Non-substrate | 0.7627 |
| CYP450 3A4 Substrate | Substrate | 0.5833 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8172 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8023 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8543 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7845 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.7359 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9423 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9421 |
| Non-inhibitor | 0.5929 | |
| AMES Toxicity | Non AMES toxic | 0.6725 |
| Carcinogens | Non-carcinogens | 0.8945 |
| Fish Toxicity | High FHMT | 0.9845 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9751 |
| Honey Bee Toxicity | Low HBT | 0.6326 |
| Biodegradation | Not ready biodegradable | 0.9949 |
| Acute Oral Toxicity | III | 0.5687 |
| Carcinogenicity (Three-class) | Non-required | 0.6066 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.3072 | LogS |
| Caco-2 Permeability | -0.3817 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.8516 | LD50, mol/kg |
| Fish Toxicity | 1.4768 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.4935 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Hyperpolarization by N-(3-oxododecanoyl)-l-homoserine-lactone, a quorum sensing molecule, in rat thymic lymphocytes. | Chem Biol Interact | 2018 Mar 1 | 29427588 |
| Diet supplementation with rice bran enzymatic extract restores endothelial impairment and wall remodelling of ApoE(-/-) mice microvessels. | Atherosclerosis | 2016 Jul | 27175607 |
| Evidence for the Involvement of Potassium Channel Inhibition in the Antidepressant-Like Effects of Hesperidin in the Tail Suspension Test in Mice. | J Med Food | 2015 Jul | 25647144 |
| Mechanisms of vasorelaxation induced by oleoylethanolamide in the rat small mesenteric artery. | Eur J Pharmacol | 2013 Feb 28 | 23340219 |
| Role of potassium channels in the antidepressant-like effect of folic acid in the forced swimming test in mice. | Pharmacol Biochem Behav | 2012 Mar | 22227220 |
| Comparison between a TaqMan polymerase chain reaction assay and a culture method for ctx-positive Vibrio cholerae detection. | J Agric Food Chem | 2010 Apr 14 | 20229998 |
| Endothelium-independent vasodilation induced by kolaviron, a biflavonoid complex from Garcinia kola seeds, in rat superior mesenteric arteries. | J Smooth Muscle Res | 2009 Feb | 19377272 |
| Galactooligosaccharides (GOS) inhibit Vibrio cholerae toxin binding to its GM1 receptor. | J Agric Food Chem | 2009 Apr 22 | 19290638 |
| Dietary soy modulates endothelium-dependent relaxation in aged male rats: Increased agonist-induced endothelium-derived hyperpolarising factor and basal nitric oxide activity. | Free Radic Biol Med | 2006 Sep 1 | 16895793 |
| Excitation, inhibition, and suppression by odors in isolated toad and rat olfactory receptor neurons. | Am J Physiol Cell Physiol | 2000 Jul | 10898714 |
Targets
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Increases the apparent Ca(2+)/voltage sensitivity of the KCNMA1 channel. It also modifies KCNMA1 channel kinetics and alters its pharmacological properties. It slows down the activation and the deactivation kinetics of the channel. Acts as a negative regulator of smooth muscle contraction by enhancing the calcium sensitivity to KCNMA1. Its presence is also a requirement for internal binding of the KCNMA1 channel opener dehydrosoyasaponin I (DHS-1) triterpene glycoside and for external binding of the agonist hormone 17-beta-estradiol (E2). Increases the binding activity of charybdotoxin (CTX) toxin to KCNMA1 peptide blocker by increasing the CTX association rate and decreasing the dissociation rate.
- Gene Name:
- KCNMB1
- Uniprot ID:
- Q16558
- Molecular Weight:
- 21797.27 Da
- Mechanism of Action:
- Charybdotoxin blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability.
References
- 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 ]
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Acts as a negative regulator that confers rapid and complete inactivation of KCNMA1 channel complex. May participate in KCNMA1 inactivation in chromaffin cells of the adrenal gland or in hippocampal CA1 neurons.
- Gene Name:
- KCNMB2
- Uniprot ID:
- Q9Y691
- Molecular Weight:
- 27129.37 Da
- Mechanism of Action:
- Charybdotoxin blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability.
References
- 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 ]
- General Function:
- Protein phosphatase binding
- Specific Function:
- Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:26148990). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin (PubMed:17157250, PubMed:18796614).
- Gene Name:
- KCNN4
- Uniprot ID:
- O15554
- Molecular Weight:
- 47695.12 Da
- Mechanism of Action:
- Charybdotoxin blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability.
References
- 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 ]
- General Function:
- Voltage-gated ion channel activity
- Specific Function:
- Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
- Gene Name:
- KCNA3
- Uniprot ID:
- P22001
- Molecular Weight:
- 63841.09 Da
- Mechanism of Action:
- Charybdotoxin blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability.
References
- 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 ]
- General Function:
- Small conductance calcium-activated potassium channel activity
- Specific Function:
- Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin (By similarity).
- Gene Name:
- KCNN1
- Uniprot ID:
- Q92952
- Molecular Weight:
- 59986.87 Da
- Mechanism of Action:
- Charybdotoxin blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability.
References
- 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 ]
- General Function:
- Small conductance calcium-activated potassium channel activity
- Specific Function:
- Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
- Gene Name:
- KCNN2
- Uniprot ID:
- Q9H2S1
- Molecular Weight:
- 63759.03 Da
- Mechanism of Action:
- Charybdotoxin blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability.
References
- 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 ]
- General Function:
- Small conductance calcium-activated potassium channel activity
- Specific Function:
- Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
- Gene Name:
- KCNN3
- Uniprot ID:
- Q9UGI6
- Molecular Weight:
- 82025.305 Da
- Mechanism of Action:
- Charybdotoxin blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability.
References
- 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 ]
- General Function:
- Voltage-gated potassium channel activity
- Specific Function:
- Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).
- Gene Name:
- KCNMA1
- Uniprot ID:
- Q12791
- Molecular Weight:
- 137558.115 Da
- Mechanism of Action:
- Charybdotoxin blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability.
References
- 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 ]
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Alters the functional properties of the current expressed by the KCNMA1 channel. Isoform 2, isoform 3 and isoform 4 partially inactivate the current of KCNBMA. Isoform 4 induces a fast and incomplete inactivation of KCNMA1 channel that is detectable only at large depolarizations. In contrast, isoform 1 does not induce detectable inactivation of KCNMA1. Two or more subunits of KCNMB3 are required to block the KCNMA1 tetramer.
- Gene Name:
- KCNMB3
- Uniprot ID:
- Q9NPA1
- Molecular Weight:
- 31603.26 Da
- Mechanism of Action:
- Charybdotoxin blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability.
References
- 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 ]
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations.
- Gene Name:
- KCNMB4
- Uniprot ID:
- Q86W47
- Molecular Weight:
- 23948.465 Da
- Mechanism of Action:
- Charybdotoxin blocks calcium-activated and voltage gated potassium channels by binding to one of four independent, overlapping binding sites. This results in neuronal hyperexcitability.
References
- 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 ]