Iberiotoxin
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Basic Info
| Common Name | Iberiotoxin(F04707) |
| 2D Structure | |
| Description | Iberiotoxin is a peptide toxin produced by the Eastern Indian red scorpion (Buthus tamulus). It selectively inhibits the current through large-conductance calcium-activated potassium channels. (L1050) |
| FRCD ID | F04707 |
| CAS Number | 129203-60-7 |
| PubChem CID | 71433880 |
| Formula | C83H133N29O27S4 |
| IUPAC Name | None |
| InChI Key | PVLXIJSXQQLSEN-UHFFFAOYSA-N |
| InChI | InChI=1S/C83H133N29O27S4/c1-42(2)28-50-76(133)107-51(29-44-14-6-5-7-15-44)70(127)98-38-65(121)112-68(43(3)4)80(137)109-53(31-67(124)125)77(134)104-45(18-12-25-91-82(87)88)69(126)97-36-63(119)101-47(17-9-11-24-85)74(131)110-54(39-141-140-27-22-58(114)100-46(16-8-10-23-84)73(130)108-52(30-66(122)123)78(135)106-50)71(128)96-34-61(117)94-32-59(115)93-33-60(116)95-35-62(118)103-56-41-143-142-40-55(111-75(132)48(105-79(56)136)19-13-26-92-83(89)90)72(129)99-37-64(120)102-49(81(138)139)20-21-57(86)113/h5-7,14-15,42-43,45-56,68H,8-13,16-41,84-85H2,1-4H3,(H2,86,113)(H,93,115)(H,94,117)(H,95,116)(H,96,128)(H,97,126)(H,98,127)(H,99,129)(H,100,114)(H,101,119)(H,102,120)(H,103,118)(H,104,134)(H,105,136)(H,106,135)(H,107,133)(H,108,130)(H,109,137)(H,110,131)(H,111,132)(H,112,121)(H,122,123)(H,124,125)(H,138,139)(H4,87,88,91)(H4,89,90,92) |
| Canonical SMILES | CC(C)CC1C(=O)NC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NCC(=O)NC(C(=O)NC(CSSCCC(=O)NC(C(=O)NC(C(=O)N1)CC(=O)O)CCCCN)C(=O)NCC(=O)NCC(=O)NCC(=O)NCC(=O)NC2CSSCC(NC(=O)C(NC2=O)CCCNC(=N)N)C(=O)NCC(=O)NC(CCC(=O)N)C(=O)O)CCCCN)CCCNC(=N)N)CC(=O)O)C(C)C)CC3=CC=CC=C3 |
| Isomeric SMILES | CC(C)CC1C(=O)NC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NCC(=O)NC(C(=O)NC(CSSCCC(=O)NC(C(=O)NC(C(=O)N1)CC(=O)O)CCCCN)C(=O)NCC(=O)NCC(=O)NCC(=O)NCC(=O)NC2CSSCC(NC(=O)C(NC2=O)CCCNC(=N)N)C(=O)NCC(=O)NC(CCC(=O)N)C(=O)O)CCCCN)CCCNC(=N)N)CC(=O)O)C(C)C)CC3=CC=CC=C3 |
| Synonyms |
CTK8E9594
|
| 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 heteromonocyclic compounds |
| Substituents | Polypeptide - Cyclic alpha peptide - Glutamine or derivatives - N-acyl-alpha-amino acid - N-acyl-alpha amino acid or derivatives - Macrolactam - Alpha-amino acid amide - N-substituted-alpha-amino acid - Alpha-amino acid or derivatives - Tricarboxylic acid or derivatives - Monocyclic benzene moiety - Fatty acyl - Benzenoid - Fatty amide - Secondary carboxylic acid amide - Primary carboxylic acid amide - Guanidine - Lactam - Carboxamide group - Organic disulfide - Amino acid - Amino acid or derivatives - Azacycle - Carboxylic acid derivative - Carboxylic acid - Organoheterocyclic compound - Carboximidamide - Organic oxide - Amine - Organopnictogen compound - Organic oxygen compound - Organic nitrogen compound - Carbonyl group - Hydrocarbon derivative - Primary amine - Imine - Organooxygen compound - Organonitrogen compound - Primary aliphatic amine - Aromatic heteromonocyclic 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 | 2097.393 |
| Hydrogen Bond Donor Count | 32 |
| Hydrogen Bond Acceptor Count | 35 |
| Rotatable Bond Count | 45 |
| Complexity | 4410 |
| Monoisotopic Mass | 2095.881 |
| Exact Mass | 2095.881 |
| XLogP | -14 |
| Formal Charge | 0 |
| Heavy Atom Count | 143 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 13 |
| 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- | 0.9463 |
| Human Intestinal Absorption | HIA- | 0.5000 |
| Caco-2 Permeability | Caco2- | 0.7012 |
| P-glycoprotein Substrate | Substrate | 0.8739 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8402 |
| Non-inhibitor | 0.9814 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9193 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6679 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7523 |
| CYP450 2D6 Substrate | Non-substrate | 0.7850 |
| CYP450 3A4 Substrate | Non-substrate | 0.5392 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8286 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8286 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8981 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7876 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8630 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9741 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9386 |
| Non-inhibitor | 0.7646 | |
| AMES Toxicity | Non AMES toxic | 0.7101 |
| Carcinogens | Non-carcinogens | 0.9123 |
| Fish Toxicity | High FHMT | 0.9595 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9797 |
| Honey Bee Toxicity | Low HBT | 0.7045 |
| Biodegradation | Not ready biodegradable | 0.9959 |
| Acute Oral Toxicity | III | 0.5532 |
| Carcinogenicity (Three-class) | Non-required | 0.6077 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.4483 | LogS |
| Caco-2 Permeability | -0.6202 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.8293 | LD50, mol/kg |
| Fish Toxicity | 1.6481 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.3693 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| AKAP150 contributes to enhanced vascular tone by facilitating large-conductance Ca2+-activated K+ channel remodeling in hyperglycemia and diabetes mellitus. | Circ Res | 2014 Feb 14 | 24323672 |
| Mechanisms of vasorelaxation induced by oleoylethanolamide in the rat small mesenteric artery. | Eur J Pharmacol | 2013 Feb 28 | 23340219 |
| Maturation of spiking activity in trout retinal ganglion cells coincides with upregulation of Kv3.1- and BK-related potassium channels. | J Neurosci Res | 2004 Jan 1 | 14689447 |
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:
- Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels with high affinity. It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel.
References
- Wikipedia. Iberiotoxin. Last Updated 24 June 2009. : http://en.wikipedia.org/wiki/Iberiotoxin
- 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:
- Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels with high affinity. It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel.
References
- Wikipedia. Iberiotoxin. Last Updated 24 June 2009. : http://en.wikipedia.org/wiki/Iberiotoxin
- 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:
- Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels with high affinity. It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel.
References
- Wikipedia. Iberiotoxin. Last Updated 24 June 2009. : http://en.wikipedia.org/wiki/Iberiotoxin
- 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:
- Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels with high affinity. It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel.
References
- Wikipedia. Iberiotoxin. Last Updated 24 June 2009. : http://en.wikipedia.org/wiki/Iberiotoxin
- 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:
- Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels with high affinity. It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel.
References
- Wikipedia. Iberiotoxin. Last Updated 24 June 2009. : http://en.wikipedia.org/wiki/Iberiotoxin