Review Article

Melittin, a Potential Natural Toxin of Crude Bee Venom: Probable Future Arsenal in the Treatment of Diabetes Mellitus

Table 1

Principal honeybee protein (melittin).

Bee venom protein nameMelittin
Alternative namesAllergen Api m 3, Allergen Api m III, Allergen Api m 4
Percentage of dry weight (%)40–50
Sources
 HoneybeeApis mellifera (honeybee), Apis mellifera carnica (Carniolan honeybee), Apis dorsata (giant honeybee), Apis florea (dwarf honeybee), Apis cerana (Indian honeybee)
 BeeOsmia rufa (red mason bee)
 InsectVespa magnifica (hornet), Polistes hebraeus (paper wasp), Polistes sp. (golden paper wasp), Vespula maculifrons (eastern yellow jacket), Vespa velutina nigrithorax (hornet)
 BacteriaSalmonella typhi, Pseudomonas fluorescens, Synechocystis sp., Aphanocapsa sp., Escherichia coli, Stenotrophomonas maltophilia, Pseudomonas maltophilia, Xanthomonas maltophilia, Moellerella wisconsensis, Pseudomonas batumici, Ralstonia solanacearum, Thioalkalivibrio nitratireducens, Klebsiella pneumonia, Francisella sp., Brucella melitensis biotype 1, Ralstonia solanacearum, Bacteroides xylanisolvens, Acinetobacter baumannii, Acinetobacter bereziniae, Sporomusa sp., Zunongwangia profunda, Leeuwenhoekiella blandensis, Cyclobacterium qasimii M12-11b
 OthersRana arvalis (moor frog), Rana temporaria (European common frog), Rana tagoi (Tago frog), Rana tagoi okiensis (Oki brown frog), Rana sakuraii (Japanese brown frog), Naja oxiana (Central Asian Cobra) (Oxus cobra), Pardachirus pavoninus (peacock sole)
Tissue specificityExpressed by the venom gland
Gene nameMELT
FormulaC350H552N84099S2
Total number of atoms1087
Molecular weight (Dalton)7584.8
Total length (amino acids)70
Peptide length (amino acids)26
Total sequence10: MKFLVNVALV, 20: FMVVYISYIY, 30: AAPEPEPAPE, 40: PEAEADAEAD, 50: PEAGIGAVLK, 60: VLTTGLPALI, 70: SWIKRKRQQG
Peptide sequence44–69: GIGAVLKVLTTGLPALISWIKRKRQQ
Theoretical isoelectric point (pI)4.69
SubunitMonomer and homotetramer
Total number of negatively charged residues (Asp + Glu)9
Total number of positively charged residues (Arg + Lys)6
Extinction coefficient
(M−1cm−1)
9970, at 280 nm measured in water
Estimated half-life(i) 30 hours (mammalian reticulocytes, in vitro)
(ii) >20 hours (yeast, in vivo)
(iii) >10 hours (Escherichia coli, in vivo)
Grand average of hydropathicity (GRAVY)0.239
Toxic doseLC (50) is 2.7 µg/mL against killifish
Investigated biological functions
 Major(i) Hemolytic activity
(ii) Anti-inflammatory activity
(iii) Anticancer, antibacterial, antifungal, antiviral activities
 Others(i) Inhibits well-known transport pumps (such as Na+-K+-ATPase, H+-K+-ATPase)
(ii) Activates phospholipase A2
(iii) Diminishes membrane surface tension
(iv) Stimulates smooth muscle
(v) Lowers blood coagulation
(vi) Influences central nervous system (CNS)
(vii) Increases capillary permeability
Adverse effects(i) Initiates various allergic reactions
(ii) Lyses erythrocytes
(iii) Creates cytotoxicity in human peripheral blood lymphocytes
(iv) Modulates gene expression related to apoptosis, DNA damage response, and oxidative stress
Medical applications(i) Arthritis
(ii) Cancer
(iii) Diseases of central and peripheral nervous systems
(iv) Skin diseases
(v) Heart and blood system related diseases
(vi) Frozen shoulder
(vii) Asthma, bronchitis
(viii) Colitis, ulcers
(xi) Others: ophthalmology, endocrinology, urology, gynecology, otorhinolaryngology
Data sources and references(i) Research Collaboratory for Structural Bioinformatics, Protein Data Bank (RCSB PDB)
(ii) Protein Information Resource (PIR)
(iii) UniprotKB
(iv) [519]

Note. Lethal concentration: LC, three-dimensional: 3D, and nuclear magnetic resonance: NMR.