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Latest revision as of 14:26, 15 July 2024 edit undoZefr (talk | contribs)Extended confirmed users, Pending changes reviewers69,458 edits →Toxicity of a bee sting: overinterpretation as toxicity caused only by melattin; sources are individual case reports, not WP:BMI reviews; update Drugs.com ref |
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{{Infobox protein family |
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| Symbol = Melittin |
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| Name = Melittin |
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| image = PDB 2mlt EBI.jpg |
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| width = |
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| caption = Melittin |
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| Pfam = PF01372 |
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| Pfam_clan = |
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| InterPro = IPR002116 |
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| SMART = |
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| PROSITE = |
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| MEROPS = |
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| SCOP = 2mlt |
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| TCDB = 1.C.18 |
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| OPM family = 151 |
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| OPM protein = 2mlt |
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| CAZy = |
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| CDD = |
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}} |
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{{chembox |
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{{chembox |
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| Verifiedfields = changed |
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|ImageFile=Melitten.svg |
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| Watchedfields = changed |
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|ImageSize=275px |
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| verifiedrevid = 414059490 |
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|IUPACName= |
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| ImageFile= |
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|OtherNames= |
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| ImageSize=275px |
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|Reference=<ref>, ].</ref> |
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| IUPACName= |
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| OtherNames= |
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| Reference=<ref>, ].</ref> |
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|Section1={{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| CASNo_Ref = {{cascite|correct|??}} |
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| CASNo=20449-79-0 |
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| CASNo=20449-79-0 |
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| PubChem=16129627 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| SMILES=CCC(C)C(C(=O)NCC(=O)NC(C)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(C(C)O)C(=O)NCC(=O)NC(CC(C)C)C(=O)N1CCCC1C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(C(C)CC)C(=O)NC(CO)C(=O)NC(CC2=CNC3=CC=CC=C32)C(=O)NC(C(C)CC)C(=O)NC(CCCCN)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCCN)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCC(=O)N)C(=O)NC(CCC(=O)N)C(=O)N)NC(=O)CN |
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| ChEBI = 6736 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 412927 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = 24VT8NVE75 |
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| PubChem = 16133648 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 17290230 |
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| SMILES = CCC(C)C(C(=O)NCC(=O)NC(C)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(C(C)O)C(=O)NCC(=O)NC(CC(C)C)C(=O)N1CCCC1C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(C(C)CC)C(=O)NC(CO)C(=O)NC(Cc2cc3c2cccc3)C(=O)NC(C(C)CC)C(=O)NC(CCCCN)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCCN)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCC(=O)N)C(=O)NC(CCC(=O)N)C(=O)N)NC(=O)CN |
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| InChI = 1/C131H229N39O31/c1-23-71(16)102(163-97(176)60-135)122(194)146-62-98(177)148-74(19)109(181)164-100(69(12)13)124(196)160-88(55-65(4)5)116(188)155-84(41-30-33-51-134)115(187)165-101(70(14)15)125(197)161-90(57-67(8)9)118(190)168-106(77(22)173)128(200)169-105(76(21)172)123(195)147-63-99(178)150-92(58-68(10)11)129(201)170-54-36-44-94(170)121(193)149-75(20)108(180)158-89(56-66(6)7)117(189)166-104(73(18)25-3)127(199)162-93(64-171)120(192)159-91(59-78-61-145-80-38-27-26-37-79(78)80)119(191)167-103(72(17)24-2)126(198)157-83(40-29-32-50-133)111(183)154-85(42-34-52-143-130(139)140)112(184)152-82(39-28-31-49-132)110(182)153-86(43-35-53-144-131(141)142)113(185)156-87(46-48-96(137)175)114(186)151-81(107(138)179)45-47-95(136)174/h26-27,37-38,61,65-77,81-94,100-106,145,171-173H,23-25,28-36,39-60,62-64,132-135H2,1-22H3,(H2,136,174)(H2,137,175)(H2,138,179)(H,146,194)(H,147,195)(H,148,177)(H,149,193)(H,150,178)(H,151,186)(H,152,184)(H,153,182)(H,154,183)(H,155,188)(H,156,185)(H,157,198)(H,158,180)(H,159,192)(H,160,196)(H,161,197)(H,162,199)(H,163,176)(H,164,181)(H,165,187)(H,166,189)(H,167,191)(H,168,190)(H,169,200)(H4,139,140,143)(H4,141,142,144)/t71-,72-,73-,74-,75-,76+,77+,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,100-,101-,102-,103-,104-,105-,106-/m0/s1 |
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| InChIKey = VDXZNPDIRNWWCW-JFTDCZMZBB |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C131H229N39O31/c1-23-71(16)102(163-97(176)60-135)122(194)146-62-98(177)148-74(19)109(181)164-100(69(12)13)124(196)160-88(55-65(4)5)116(188)155-84(41-30-33-51-134)115(187)165-101(70(14)15)125(197)161-90(57-67(8)9)118(190)168-106(77(22)173)128(200)169-105(76(21)172)123(195)147-63-99(178)150-92(58-68(10)11)129(201)170-54-36-44-94(170)121(193)149-75(20)108(180)158-89(56-66(6)7)117(189)166-104(73(18)25-3)127(199)162-93(64-171)120(192)159-91(59-78-61-145-80-38-27-26-37-79(78)80)119(191)167-103(72(17)24-2)126(198)157-83(40-29-32-50-133)111(183)154-85(42-34-52-143-130(139)140)112(184)152-82(39-28-31-49-132)110(182)153-86(43-35-53-144-131(141)142)113(185)156-87(46-48-96(137)175)114(186)151-81(107(138)179)45-47-95(136)174/h26-27,37-38,61,65-77,81-94,100-106,145,171-173H,23-25,28-36,39-60,62-64,132-135H2,1-22H3,(H2,136,174)(H2,137,175)(H2,138,179)(H,146,194)(H,147,195)(H,148,177)(H,149,193)(H,150,178)(H,151,186)(H,152,184)(H,153,182)(H,154,183)(H,155,188)(H,156,185)(H,157,198)(H,158,180)(H,159,192)(H,160,196)(H,161,197)(H,162,199)(H,163,176)(H,164,181)(H,165,187)(H,166,189)(H,167,191)(H,168,190)(H,169,200)(H4,139,140,143)(H4,141,142,144)/t71-,72-,73-,74-,75-,76+,77+,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,100-,101-,102-,103-,104-,105-,106-/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = VDXZNPDIRNWWCW-JFTDCZMZSA-N |
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| MeSHName=Melitten |
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| MeSHName=Melitten |
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}} |
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}} |
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|Section2={{Chembox Properties |
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|Section2={{Chembox Properties |
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| Formula=C<sub>131</sub>H<sub>229</sub>N<sub>39</sub>O<sub>31</sub> |
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| Formula=C<sub>131</sub>H<sub>229</sub>N<sub>39</sub>O<sub>31</sub> |
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| MolarMass=2846.46266 |
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| MolarMass=2846.46266 |
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| Appearance= |
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| Appearance= |
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| Density= |
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| Density= |
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| MeltingPt= |
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| MeltingPt= |
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| BoilingPt= |
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| Solubility= |
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|Section3={{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| MainHazards= |
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| MainHazards= |
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| FlashPt= |
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| FlashPt= |
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| AutoignitionPt = |
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| Autoignition= |
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'''Melittin''' is the principal active component of ] (]), and is a powerful stimulator of ]. Melittin is a ] consisting of 26 ] with the sequence GIGAVLKVLTTGLPALISWIKRKRQQ. |
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'''Melittin''' is the main component (40–60% of the dry weight) and the major pain-producing substance of honeybee ('']'') ]. Melittin is a basic ] consisting of 26 ].<ref name="Chen_2016">{{cite journal | vauthors = Chen J, Guan SM, Sun W, Fu H | title = Melittin, the Major Pain-Producing Substance of Bee Venom | journal = Neuroscience Bulletin | volume = 32 | issue = 3 | pages = 265–272 | year = 2016 | pmid = 26983715 | pmc = 5563768 | doi = 10.1007/s12264-016-0024-y }}</ref> |
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==Therapeutic Use== |
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Melittin also exhibits potent anti-microbial activity. For example, Melittin has been shown to exert "profound inhibitory effects" on '']'', the ] that causes ] (). Melittin has also been shown to kill the yeast '']'' <ref>Klotz SA, Gaur NK, Rauceo J, Lake DF, Park Y, Hahm KS, Lipke PN. "" ''Antimicrobial Agents and Chemotherapy''. 2004 Nov;48(11):4337-41. PMID 15504862. Accessed November 11, 2007.</ref> and to suppress '']'' and '']'' infections. <ref>Lazarev VN, Shkarupeta MM, Titova GA, Kostrjukova ES, Akopian TA, Govorun VM. "Effect of induced expression of an antimicrobial peptide melittin on Chlamydia trachomatis and Mycoplasma hominis infections in vivo." ''Biochemical and Biophysical Research Commununications''. 2005 Dec 16;338(2):946-50. PMID 16246304</ref><ref>Lazarev VN, Stipkovits L, Biro J, Miklodi D, Shkarupeta MM, Titova GA, Akopian TA, Govorun VM. "Induced expression of the antimicrobial peptide melittin inhibits experimental infection by Mycoplasma gallisepticum in chickens." ''Microbes and Infection''. 2004 May;6(6):536-41. PMID 15158186</ref><ref>Lazarev VN, Parfenova TM, Gularyan SK, Misyurina OY, Akopian TA, Govorun VM. "Induced expression of melittin, an antimicrobial peptide, inhibits infection by Chlamydia trachomatis and Mycoplasma hominis in a HeLa cell line." ''International Journal of Antimicrobial Agents''. 2002 Feb;19(2):133-7. PMID 11850166</ref> |
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== Function == |
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At Washington University School of Medicine in St. Louis, very small nanite "nanobee" devices are being used to carefully deliver melittin, which is known to disrupt cellular walls and thus destroy cells, to tumor cells.<ref>Targeting Cancer With Bee Venom""</ref> |
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The principal function of melittin as a component of ] is to cause pain and destruction of tissue of intruders that threaten a beehive. However, in honey bees, melittin is not only ] in the venom gland, but also in other tissues when infected with pathogens. The two venom molecules, melittin and ], that are over-expressed in honey bees infected with various pathogens, possibly indicate a role for melittin in the ] of bees to ]s.<ref>{{cite journal | vauthors = Doublet V, Poeschl Y, Gogol-Döring A, Alaux C, Annoscia D, Aurori C, Barribeau SM, Bedoya-Reina OC, Brown MJ, Bull JC, Flenniken ML, Galbraith DA, Genersch E, Gisder S, Grosse I, Holt HL, Hultmark D, Lattorff HM, Le Conte Y, Manfredini F, McMahon DP, Moritz RF, Nazzi F, Niño EL, Nowick K, van Rij RP, Paxton RJ, Grozinger CM | display-authors = 6 | title = Unity in defence: honeybee workers exhibit conserved molecular responses to diverse pathogens | journal = BMC Genomics | volume = 18 | issue = 1 | pages = 207 | date = March 2017 | pmid = 28249569 | pmc = 5333379 | doi = 10.1186/s12864-017-3597-6 | doi-access = free }}</ref> |
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==References== |
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{{reflist|2}} |
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==External links== |
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== Structure == |
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* {{MeshName|Melitten}} |
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Melittin is a small ] with no ]; the ''N''-terminal part of the ] is predominantly ] and the ''C''-terminal part is ] and strongly ]. In water, it forms a ] but it also can spontaneously integrate itself into cell membranes.<ref name="Terwilliger_1982">{{cite journal | vauthors = Terwilliger TC, Eisenberg D | title = The structure of melittin. II. Interpretation of the structure | journal = The Journal of Biological Chemistry | volume = 257 | issue = 11 | pages = 6016–6022 | year = 1982 | doi = 10.1016/S0021-9258(20)65098-0 | pmid = 7076662 | url = http://www.jbc.org/content/257/11/6016.full.pdf | doi-access = free }}</ref> |
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== Mechanism of action == |
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Injection of melittin into animals and humans causes pain sensation. It has strong surface effects on cell membranes causing pore-formation in ] cells and the destruction of ]s. Melittin also activates ] (pain receptor) cells through a variety of mechanisms.<ref name="Chen_2016" /> |
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Melittin can open thermal nociceptor ] channels via ] metabolites resulting in depolarization of nociceptor cells. The pore forming effects in cells causes the release of pro-inflammatory cytokines. It also activates ]-mediated opening of ]s. Finally melittin up-regulates the expression of ] and ] sodium channels in nociceptor cell causing long term action potential firing and pain sensation.<ref name="Chen_2016" /> |
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Melittin ] ] C, Ca<sup>2+</sup>/calmodulin-dependent protein ] II, ] ] ] kinase, and Na<sup>+</sup>/K<sup>+</sup>-ATPase (synaptosomal membrane). Melittin ]s ] pumps such as the Na<sup>+</sup>-K<sup>+</sup>-ATPase and the H<sup>+</sup>-K<sup>+</sup>-ATPase.<ref name="Chen_2016" /> |
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==Toxicity of a bee sting== |
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{{See also|Bee sting}} |
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Melittin is the main compound in bee venom, accounting for the potential ] of a bee sting, which causes an ] in some people.<ref name="drugs">{{cite web |title=Bee venom |url=https://www.drugs.com/npp/bee-venom.html |publisher=Drugs.com |access-date=15 July 2024 |date=2 March 2024}}</ref> At the sites of multiple stings, localized pain, swelling, and ] occur, and if bees are swallowed, life-threatening swelling of the ] and respiratory passages may develop.<ref name=drugs/> |
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==Use == |
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] has been used in ] for treating various disorders,<ref name="Rady_2917">{{cite journal | vauthors = Rady I, Siddiqui IA, Rady M, Mukhtar H | title = Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy | journal = Cancer Letters | volume = 402 | pages = 16–31 | year = 2017 | pmid = 28536009 | pmc = 5682937 | doi = 10.1016/j.canlet.2017.05.010 }}</ref> although its non-specific ] has limited ] on its potential effects.<ref name="Liu_2016">{{cite journal | vauthors = Liu CC, Hao DJ, Zhang Q, An J, Zhao JJ, Chen B, Zhang LL, Yang H | title = Application of bee venom and its main constituent melittin for cancer treatment | journal = Cancer Chemotherapy and Pharmacology | volume = 78 | issue = 6 | pages = 1113–1130 | year = 2016 | pmid = 27677623 | doi = 10.1007/s00280-016-3160-1 | s2cid = 12596298 }}</ref> |
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== References == |
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{{reflist|32em}} |
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== External links == |
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* {{MeshName|Melitten}} |
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{{Pharma-stub}} |
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{{Membrane proteins}} |
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{{Membrane proteins}} |
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{{Pore-forming toxins}} |
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{{Pore-forming toxins}} |
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