Agelenin

Last updated
Agelenin
Names
Other names
U1-agatoxin-Aop1a, U1-AGTX-Aop1a
Identifiers
3D model (JSmol)
ChemSpider
  • none
KEGG
  • InChI=1S/C160H259N51O46S6/c1-14-82(12)126(155(254)197-99(55-85-61-176-88-32-19-18-31-87(85)88)141(240)195-103(59-125(224)225)144(243)202-108(68-214)145(244)186-92(36-25-45-174-159(168)169)133(232)205-113(73-261)150(249)199-105(157(256)257)53-81(10)11)209-146(245)109(69-215)203-139(238)97(51-79(6)7)191-135(234)94(40-41-124(222)223)188-130(229)89(33-20-22-42-161)187-148(247)111(71-259)204-132(231)90(34-21-23-43-162)184-137(236)95(49-77(2)3)182-122(220)64-178-128(227)106(66-212)201-151(250)114(74-262)208-152(251)115(75-263)206-134(233)93(37-26-46-175-160(170)171)189-153(252)116-38-27-47-210(116)123(221)65-179-129(228)107(67-213)200-138(237)96(50-78(4)5)190-127(226)83(13)181-136(235)101(57-118(164)216)194-149(248)112(72-260)207-140(239)98(54-84-29-16-15-17-30-84)192-131(230)91(35-24-44-173-158(166)167)185-143(242)102(58-119(165)217)193-142(241)100(56-86-62-172-76-180-86)196-154(253)117-39-28-48-211(117)156(255)104(52-80(8)9)198-147(246)110(70-258)183-121(219)63-177-120(218)60-163/h15-19,29-32,61-62,76-83,89-117,126,176,212-215,258-263H,14,20-28,33-60,63-75,161-163H2,1-13H3,(H2,164,216)(H2,165,217)(H,172,180)(H,177,218)(H,178,227)(H,179,228)(H,181,235)(H,182,220)(H,183,219)(H,184,236)(H,185,242)(H,186,244)(H,187,247)(H,188,229)(H,189,252)(H,190,226)(H,191,234)(H,192,230)(H,193,241)(H,194,248)(H,195,240)(H,196,253)(H,197,254)(H,198,246)(H,199,249)(H,200,237)(H,201,250)(H,202,243)(H,203,238)(H,204,231)(H,205,232)(H,206,233)(H,207,239)(H,208,251)(H,209,245)(H,222,223)(H,224,225)(H,256,257)(H4,166,167,173)(H4,168,169,174)(H4,170,171,175)/t82-,83-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,126-/m0/s1
    Key: ZUAKRHLBADVPFO-XJXDTQAOSA-N
  • NCC(=O)NCC(=O)N[C@@]([H])(CS)C(=O)N[C@@]([H])(CC(C)C)C(=O)N1[C@@]([H])(CCC1)C(=O)N[C@@]([H])(CC1=CN=C-N1)C(=O)N[C@@]([H])(CC(=O)N)C(=O)N[C@@]([H])(CCCNC(=N)N)C(=O)N[C@@]([H])(Cc1ccccc1)C(=O)N[C@@]([H])(CS)C(=O)N[C@@]([H])(CC(=O)N)C(=O)N[C@@]([H])(C)C(=O)N[C@@]([H])(CC(C)C)C(=O)N[C@@]([H])(CO)C(=O)NCC(=O)N1[C@@]([H])(CCC1)C(=O)N[C@@]([H])(CCCNC(=N)N)C(=O)N[C@@]([H])(CS)C(=O)N[C@@]([H])(CS)C(=O)N[C@@]([H])(CO)C(=O)NCC(=O)N[C@@]([H])(CC(C)C)C(=O)N[C@@]([H])(CCCCN)C(=O)N[C@@]([H])(CS)C(=O)N[C@@]([H])(CCCCN)C(=O)N[C@@]([H])(CCC(=O)O)C(=O)N[C@@]([H])(CC(C)C)C(=O)N[C@@]([H])(CO)C(=O)N[C@@]([H])([C@]([H])(CC)C)C(=O)N[C@@]([H])(CC(=CN2)C1=C2C=CC=C1)C(=O)N[C@@]([H])(CC(=O)O)C(=O)N[C@@]([H])(CO)C(=O)N[C@@]([H])(CCCNC(=N)N)C(=O)N[C@@]([H])(CS)C(=O)N[C@@]([H])(CC(C)C)C(=O)O
Properties
Molar mass 3500 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Agelenin, also called U1-agatoxin-Aop1a, [1] is an antagonist of the presynaptic P-type calcium channel in insects. This neurotoxic peptide consists of 35 amino acids and can be isolated from the venom of the spider Allagelena opulenta .

Contents

Sources

Agelenin - toxicologically named as U1-agatoxin-Aop1a and abbreviated as U1-AGTX-Aop1a - is an insecticidal toxin of the venom of the species Allagelena opulenta . [2] It was first discovered in 1990. [3]

Chemistry

Agelenin consists of a polypeptide chain of 35 amino acid residues. [3] It has a short anti-parallel β-sheet connected by three disulfide bonds and four β-turns that form the compact core structure. The three amino acid residues that are thought to be essential for the inhibiting activity of agelenin are Phe9, Ser28 and Arg33. [4]

The structure of agelenin is similar to the structure of ICK toxins like ω-Aga-IVA and ω-ACTXHv1a in that they all consist of three disulfide bonds with the same bonding pattern. An important difference between agelenin and ω-Aga-IVA and ω-ACTXHv1a is that ω-Aga-IVA and ω-ACTXHv1a have functional C-terminal tails. [4]

Agelenin belongs to toxin group of Agatoxins. [2] The amino acid structure of agelenin is Gly-Gly-Cys-Leu-Pro-His-Asn-Arg-Phe-Cys-Asn-Ala-Leu-Ser-Gly-Pro-Arg-Cys-Cys-Ser-Gly-Leu-Lys-Cys-Lys-Glu-Leu-Ser-Ile-Trp-Asp-Ser-Arg-Cys-Leu (GGCLPHNRFCNALSGPRCCSGLKCKELSIWDSRCL). [4]

Target

Agelenin is directed against P-subtype calcium channels in insects. [5]

Toxicity

Agelenin is not toxic in mammals, but has a PD50 of 291 pmol/g in crickets where it causes rapid, reversible paralysis. [4] In preparations of neuromuscular junctions of lobsters agelenin causes a non-reversible paralysis due to the suppression of excitatory postsynaptic potentials, presumably by inhibition of the presynaptic calcium influx. [3]

Related Research Articles

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Delta atracotoxin

Delta atracotoxin is a low-molecular-weight neurotoxic polypeptide found in the venom of the Sydney funnel-web spider.

omega-Grammotoxin SIA (ω-grammotoxin SIA) is a protein toxin that inhibits P, Q, and N voltage-gated calcium channels (Ca2+ channels) in neurons.

Agitoxin

Agitoxin is a toxin found in the venom of the scorpion Leiurus quinquestriatus hebraeus. Other toxins found in this species include charybdotoxin (CTX). CTX is a close homologue of Agitoxin.

Grammotoxin

Grammotoxin is a toxin in the venom of the tarantula Grammostola spatulata. It is a protein toxin that inhibits P-, Q- and N-type voltage-gated calcium channels in neurons. Grammotoxin is also known as omega-grammotoxin SIA.

Neurophysin II

Neurophysin II is a carrier protein with a size of 19,687.3 Da and is made up of a dimer of two virtually identical chains of amino acids. Neurophysin II is a cleavage product of the AVP gene. It is a neurohypophysial hormone that is transported in vesicles with vasopressin, the other cleavage product, along axons, from magnocellular neurons of the hypothalamus to the posterior lobe of the pituitary. Although it is stored in neurosecretory granules with vasopressin and released with vasopressin into the bloodstream, its biological action is unclear. Neurophysin II is also known as a stimulator of prolactin secretion.

The P-type calcium channel is a type of voltage-dependent calcium channel. Similar to many other high-voltage-gated calcium channels, the α1 subunit determines most of the channel's properties. The 'P' signifies cerebellar Purkinje cells, referring to the channel's initial site of discovery. P-type calcium channels play a similar role to the N-type calcium channel in neurotransmitter release at the presynaptic terminal and in neuronal integration in many neuronal types.

Agatoxin

Agatoxins are a class of chemically diverse polyamine and peptide toxins which are isolated from the venom of various spiders. Their mechanism of action includes blockade of glutamate-gated ion channels, voltage-gated sodium channels, or voltage-dependent calcium channels. Agatoxin is named after the funnel web spider which produces a venom containing several agatoxins. There are different agatoxins. The ω‎-agatoxins are approximately 100 amino acids in length and are antagonists of voltage-sensitive calcium channels and also block the release of neurotransmitters. For instance, the ω‎-agatoxin 1A is a selective blocker and will block L-type calcium channels whereas the ω‎-agatoxin 4B will inhibit voltage sensitive P-type calcium channels. The μ‎-agatoxins only act on insect voltage-gated sodium channels.

Pompilidotoxin is a toxin from the venom of spider wasps that slows the inactivation of Na+channels.

BeKm-1 is a toxin from the Central Asian scorpion Buthus eupeus. BeKm-1 acts by selectively inhibiting the human Ether-à-go-go Related Gene (hERG) channels, which are voltage gated potassium ion channels.

Guangxitoxin

Guangxitoxin, also known as GxTX, is a peptide toxin found in the venom of the tarantula Plesiophrictus guangxiensis. It primarily inhibits outward voltage-gated Kv2.1 potassium channel currents, which are prominently expressed in pancreatic β-cells, thus increasing insulin secretion.

Hanatoxin is a toxin found in the venom of the Grammostola spatulata tarantula. The toxin is mostly known for inhibiting the activation of voltage-gated potassium channels, most specifically Kv4.2 and Kv2.1, by raising its activation threshold.

Hainantoxins (HNTX) are neurotoxins from the venom of the Chinese bird spider Haplopelma hainanum. Hainantoxins specifically inhibit tetrodotoxin-sensitive Voltage-gated sodium channels, thereby causing blockage of neuromuscular transmission and paralysis. Currently, 13 different hainantoxins are known, but only HNTX-I, -II, -III, -IV and -V have been investigated in detail.

Huwentoxins (HWTX) are a group of neurotoxic peptides found in the venom of the Chinese bird spider Haplopelma schmidti. The species was formerly known as Haplopelma huwenum, Ornithoctonus huwena and Selenocosmia huwena. While structural similarity can be found among several of these toxins, HWTX as a group possess high functional diversity.

Centruroides suffusus suffusus toxin II (CssII) is a scorpion β-toxin from the venom of the scorpion Centruroides suffusus suffusus. CssII primarily affects voltage-gated sodium channels by causing a hyperpolarizing shift of voltage dependence, a reduction in peak transient current, and the occurrence of resurgent currents.

HgeTx1 (systematic name: α-KTx 6.14) is a toxin produced by the Mexican scorpion Hoffmanihadrurus gertschi that is a reversible blocker of the Shaker B K+-channel, a type of voltage-gated potassium channels.

Vejocalcin

Vejocalcin (VjCa, also called Vejocalcine) is a toxin from the venom of the Mexican scorpion Vaejovis mexicanus. Vejocalcin is a member of the calcin family of toxins. It acts as a cell-penetrating peptide (CPP); it binds with high affinity and specificity to skeletal ryanodine receptor 1 (RYR1) of the sarcoplasmic reticulum, thereby triggering calcium release from intracellular Ca2+ stores.

LmαTX5 is an α-scorpion toxin which inhibits the fast inactivation of voltage-gated sodium channels. It has been identified through transcriptome analysis of the venom gland of Lychas mucronatus, also known as the Chinese swimming scorpion – a scorpion species which is widely distributed in Southeast Asia.

DKK-Sp1

DKK-SP1 is one of the 100,000 toxins present in the Buthusmartensii Karsch. scorpion. DKK-SP1 targets the voltage-gated Sodium channel Nav1.8, and exerts its effect on it by inhibiting its current. It has been used in traditional Chinese medicine for centuries for treating many diseases

Prototoxin-1, or Beta/omega-theraphotoxin-Tp1a, is a 35-amino-acid peptide neurotoxin extracted from the venom of the tarantula Thrixopelma pruriens. Prototoxin-1 belongs to the inhibitory cystine knot (ICK) family of peptide toxins, which have been known to potently inhibit voltage-gated ion channels. Prototoxin-1 selectively blocks low voltage threshold “T-type” calcium channels., voltage gated sodium channels and the nociceptor cation channel TRPA1. Due to its unique ability to bind to TRPA1, Prototoxin-1 has been implicated as a valuable pharmacological reagent with potential applications in clinical contexts with regards to pain and inflammation

References

  1. ↑ Institute for Molecular Bioscience. (2010) “U2-agatoxin-Aop1a”, Arachnoserver. Accessed on: 11 October 2015.
  2. 1 2 Institute for Molecular Bioscience. (2010) “U2-agatoxin-Ao1a”, Arachnoserver. Accessed on: 11 October 2015.
  3. 1 2 3 Hagiwara, K., Sakai, T., Miwa, A., Kawai, N. and Nakajima, T. (1990) “Complete amino acid sequence of a new type of neurotoxin from the venom of the spider, Agelena opulenta”, BioMed Research International, vol. 11, pp. 181-186.
  4. 1 2 3 4 Yamaji, N., Sugase, K., Nakajima, T., Miki, T., Wakamori, M., More, Y. and Iwashita, T. (2007) “Solution structure of agelenin, an intisecticidal peptide isolated from the spider Agelena opulenta, and its structural similarities to insect-specific calcium channel inhibitors”, FEBS Letters, vol. 20, pp. 3789-3794.
  5. ↑ Rash, L.D. and Hodgson, W.C. (2002) “Pharmacology and biochemistry of spider venoms”, Toxicon, vol. 40, pp. 225-254.
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