Slotoxin

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Slotoxin
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
  • 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 ☒N
    Key: ZVNHBACJFBOPKF-UTPLJIOFSA-N ☒N
  • 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.

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

Toxicity

References

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