Melittin

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Melittin
PDB 2mlt EBI.jpg
Melittin
Identifiers
SymbolMelittin
PfamPF01372
InterProIPR002116
SCOP2mlt
SUPERFAMILY2mlt
TCDB1.C.18
OPM superfamily151
OPM protein2mlt
Melittin[1]
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.157.496
MeSH Melitten
UNII
Properties
C131H229N39O31
Molar mass 2846.46266
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Melittin is the main component (40–60% of the dry weight) and the major pain producing substance of honeybee (Apis mellifera) venom . Melittin is a basic peptide consisting of 26 amino acids.[2]

Function[edit]

The principal function of melittin as a component of bee venom is to cause pain and destruction of tissue of intruders that threaten bees hive. However in honey bees, melittin is not only expressed in the venom gland, but also in other tissues when infected with pathogens. The two venom molecules, melittin and secapin, are over-expressed in honey bees infected with various pathogens, possibly indicating a role for melittin in the immune response of bees to infectious diseases.[3]

Structure[edit]

Melittin is a small peptide with no disulfide bridge; the N-terminal part of the molecule is predominantly hydrophobic and the C-terminal part is hydrophilic and strongly basic. In water, it forms a tetramer but it also can spontaneously integrate itself into cell membranes.[4]

Mechanism of action[edit]

Injection of melittin into animals and humans causes pain sensation. It has strong surface effects on cell membranes causing pore-formation in epithelial cells and the destruction of red blood cells. Melittin also activates nociceptor (pain receptor) cells through a variety of mechanisms.[2]

Melittin can open thermal nociceptor TRPV1 channels via cyclooxygenase metabolites resulting in depolarization of nociceptor cells. The pore forming effects in cells causes the release of pro-inflammatory cytokines. It also activates G-protein-coupled receptor-mediated opening of transient receptor potential channels. Finally melittin up-regulates the expression of Nav1.8 and Nav1.9 sodium channels in nociceptor cell causing long term action potential firing and pain sensation.[2]

Melittin inhibits protein kinase C, Ca2+/calmodulin-dependent protein kinase II, myosin light chain kinase, and Na+/K+-ATPase (synaptosomal membrane). Mellitin blocks transport pumps such as the Na+-K+-ATPase and the H+-K+-ATPase. In vitro, melittin increases the permeability of cell membranes to ions,[5] particularly Na+ and indirectly Ca2+, because of the Na+-Ca2+-exchange. This effect results in morphological and functional changes, particularly in excitable tissues.[5]

Potential medical applications[edit]

Bee venom therapy has been used as a traditional medicine for the treatment of pain, inflammatory diseases, and of cancer.[6] This has motivated research into the use of the main active component of bee venom, melittin, to treat these same diseases. However the non-specific toxicity of melittin has severely limited its clinical application.[7] While melittin has been studied in in vitro and animal models for the treatment of inflammation[8] and cancer,[6][9] human efficacy data is lacking.

References[edit]

  1. ^ Melitten - Compound Summary, PubChem.
  2. ^ a b c Chen J, Guan SM, Sun W, Fu H (2016). "Melittin, the Major Pain-Producing Substance of Bee Venom". Neuroscience Bulletin. 32 (3): 265–72. doi:10.1007/s12264-016-0024-y. PMC 5563768. PMID 26983715.
  3. ^ Doublet V, Poeschl Y, Gogol-Döring A, Alaux C, Annoscia D, Aurori C, et al. (March 2017). "Unity in defence: honeybee workers exhibit conserved molecular responses to diverse pathogens". BMC Genomics. 18 (1): 207. doi:10.1186/s12864-017-3597-6. PMC 5333379. PMID 28249569.
  4. ^ Terwilliger TC, Eisenberg D (1982). "The structure of melittin. II. Interpretation of the structure" (PDF). The Journal of Biological Chemistry. 257 (11): 6016–22. PMID 7076662.
  5. ^ a b Ma R, Mahadevappa R, Kwok HF (November 2017). "Venom-based peptide therapy: insights into anti-cancer mechanism". Oncotarget. 8 (59): 100908–100930. doi:10.18632/oncotarget.21740. PMC 5725072. PMID 29246030.
  6. ^ a b Rady I, Siddiqui IA, Rady M, Mukhtar H (2017). "Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy". Cancer Letters. 402: 16–31. doi:10.1016/j.canlet.2017.05.010. PMC 5682937. PMID 28536009.
  7. ^ Liu CC, Hao DJ, Zhang Q, An J, Zhao JJ, Chen B, Zhang LL, Yang H (2016). "Application of be venom and its main constituent melittin for cancer treatment". Cancer Chemotherapy and Pharmacology. 78 (6): 1113–1130. doi:10.1007/s00280-016-3160-1. PMID 27677623.
  8. ^ Lee G, Bae H (2016). "Anti-Inflammatory Applications of Melittin, a Major Component of Bee Venom: Detailed Mechanism of Action and Adverse Effects". Molecules (Basel, Switzerland). 21 (5). doi:10.3390/molecules21050616. PMID 27187328.
  9. ^ Gajski G, Garaj-Vrhovac V (2013). "Melittin: a lytic peptide with anticancer properties". Environmental Toxicology and Pharmacology. 36 (2): 697–705. doi:10.1016/j.etap.2013.06.009. PMID 23892471.

External links[edit]