Slotoxin

Last updated
Slotoxin
Slotoxin.png
Names
IUPAC name
L-threonyl-L-phenylalanyl-L-isoleucyl-L-alpha-aspartyl-L-valyl-L-alpha-aspartyl-L-cysteinyl-L-threonyl-L-valyl-L-seryl-L-lysyl-L-alpha-glutamyl-L-cysteinyl-L-tryptophyl-L-alanyl-L-prolyl-L-cysteinyl-L-lysyl-L-alanyl-L-alanyl-L-phenylalanyl-glycyl-L-valyl-L-alpha-aspartyl-L-arginyl-glycyl-L-lysyl-L-cysteinyl-L-methionyl-glycyl-L-lysyl-L-lysyl-L-cysteinyl-L-lysyl-L-cysteinyl-L-tyrosyl-L-valine (7->28),(13->33),(17->35)-tris(disulfide)
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C177H275N47O50S7/c1-17-92(10)141(222-159(256)116(71-99-42-22-19-23-43-99)207-169(266)136(184)96(14)226)173(270)210-120(76-135(238)239)160(257)219-138(89(4)5)171(268)209-119(75-134(236)237)157(254)216-127-87-281-277-83-123-163(260)203-113(60-69-275-16)146(243)190-79-130(230)195-106(46-26-32-61-178)149(246)198-110(50-30-36-65-182)152(249)213-122-82-276-278-85-125(215-154(251)112(58-59-132(232)233)202-151(248)109(49-29-35-64-181)199-161(258)121(81-225)211-172(269)139(90(6)7)220-174(271)142(97(15)227)223-167(127)264)166(263)206-117(73-101-77-188-104-45-25-24-44-103(101)104)155(252)194-95(13)175(272)224-68-39-53-128(224)168(265)217-126(86-280-279-84-124(214-153(250)111(201-162(122)259)51-31-37-66-183)165(262)205-115(72-100-54-56-102(228)57-55-100)158(255)221-140(91(8)9)176(273)274)164(261)200-108(48-28-34-63-180)148(245)193-93(11)143(240)192-94(12)144(241)204-114(70-98-40-20-18-21-41-98)147(244)191-80-131(231)218-137(88(2)3)170(267)208-118(74-133(234)235)156(253)197-105(52-38-67-187-177(185)186)145(242)189-78-129(229)196-107(150(247)212-123)47-27-33-62-179/h18-25,40-45,54-57,77,88-97,105-128,136-142,188,225-228H,17,26-39,46-53,58-76,78-87,178-184H2,1-16H3,(H,189,242)(H,190,243)(H,191,244)(H,192,240)(H,193,245)(H,194,252)(H,195,230)(H,196,229)(H,197,253)(H,198,246)(H,199,258)(H,200,261)(H,201,259)(H,202,248)(H,203,260)(H,204,241)(H,205,262)(H,206,263)(H,207,266)(H,208,267)(H,209,268)(H,210,270)(H,211,269)(H,212,247)(H,213,249)(H,214,250)(H,215,251)(H,216,254)(H,217,265)(H,218,231)(H,219,257)(H,220,271)(H,221,255)(H,222,256)(H,223,264)(H,232,233)(H,234,235)(H,236,237)(H,238,239)(H,273,274)(H4,185,186,187)/t92-,93-,94-,95-,96+,97+,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,136-,137-,138-,139-,140-,141-,142-/m0/s1 X mark.svgN
    Key: ZVNHBACJFBOPKF-UTPLJIOFSA-N X mark.svgN
  • CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H]3CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N4CCC[C@H]4C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@@H](NC3=O)CCCCN)C(=O)N[C@@H](Cc5ccc(cc5)O)C(=O)N[C@@H](C(C)C)C(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N2)CCCCN)CCCNC(=N)N)CC(=O)O)C(C)C)Cc6ccccc6)C)C)CCCCN)C)Cc7c[nH]c8c7cccc8)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC1=O)[C@@H](C)O)C(C)C)CO)CCCCN)CCC(=O)O)CCCCN)CCCCN)CCSC)NC(=O)[C@H](Cc9ccccc9)NC(=O)[C@H]([C@@H](C)O)N
Properties
C177H281N47O50S7
Molar mass 4091.86 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Slotoxin is a peptide from Centruroides noxius Hoffmann scorpion venom. It belongs to the short scorpion toxin superfamily.

Contents

Method of isolation

For isolation of slotoxin, scorpions of the species Centruroides noxius are milked for venom in the laboratory. The crude venom is being dissolved in distilled water and spun. The supernatant is separated. The active fraction is then further separated.

Structure

The 37 amino acid peptide belongs to the charybdotoxin sub-family (αKTx1) and was numbered member 11. αKTx1.11 revealed specificity for mammalian MaxiK channels (hSlo), thus, was named slotoxin. Its sequence is H-Thr-Phe-Ile-Asp-Val-Asp-Cys(1)-Thr-Val-Ser-Lys-Glu-Cys(2)-Trp-Ala-Pro-Cys(3)-Lys-Ala-Ala-Phe-Gly-Val-Asp-Arg-Gly-Lys-Cys(1)-Met-Gly-Lys-Lys-Cys(2)-Lys-Cys(3)-Tyr-Val-OH.

Targets

Slotoxin reversibly blocks the high conductance calcium-activated potassium channels composed of only α-subunits (Kd = 1.5 nM). Unreversibly blocks the high conductance calcium-activated potassium channels composed of α- and β1-subunits. Unreversibly and weakly blocks the high conductance calcium-activated potassium channels composed of α- and β4-subunits. It shows no activity on other potassium channels.

Mode of action

The positively charged surface (C-terminal) of SloTx has a specific short-range interaction with the negatively charged pore region of potassium-channels leading to channel blockade. Specific hydrophobic residue-residue interactions between SloTx and MaxiK channels may also contribute to toxin-channel interaction. Another region in the potassium channel (flanking the N-terminal of SloTx) is situated in the face opposite to the site of toxin-pore interaction, and might have implications for the modulation of channel blockade by the MaxiK β subunits. SloTx is suggested to interact with the MaxiK channel pore-forming α-subunit by blocking the pore via a bimolecular reaction.

Toxicity

The large-conductance voltage and calcium-activated potassium (MaxiK, BK) channels are intrinsic membrane proteins that regulate excitability in a large variety of tissues including brain and smooth muscle.

Related Research Articles

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<span class="mw-page-title-main">Margatoxin</span>

Margatoxin (MgTX) is a peptide that selectively inhibits Kv1.3 voltage-dependent potassium channels. It is found in the venom of Centruroides margaritatus, also known as the Central American Bark Scorpion. Margatoxin was first discovered in 1993. It was purified from scorpion venom and its amino acid sequence was determined.

<span class="mw-page-title-main">Agitoxin</span>

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<span class="mw-page-title-main">Cobatoxin</span> Chemical compound

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<span class="mw-page-title-main">Tertiapin</span>

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<span class="mw-page-title-main">Guangxitoxin</span>

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.

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<span class="mw-page-title-main">OdK2</span>

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References

  1. "slotoxin | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY". www.guidetopharmacology.org.