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]

PDB 2mlt EBI
OPM superfamily151
OPM protein2mlt
3D model (JSmol)
ECHA InfoCard 100.157.496
MeSH Melitten
Molar mass 2846.46266
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).


The principal function of melittin as a component of bee venom is to cause pain and destruction of tissue of intruders that threaten a beehive. 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, that 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]


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

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]


Bee venom therapy has been used in traditional medicine for treating various disorders,[6] although its non-specific toxicity has limited scientific research on its potential effects.[7]


  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): 265–272. 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): 6016–6022. 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. ^ 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.

External links


Apitherapy is a branch of alternative medicine that uses honey bee products, including honey, pollen, propolis, royal jelly and bee venom. Proponents of apitherapy make claims for its health benefits which are unsupported by evidence-based medicine.


Apitoxin, or honey bee venom, is a cytotoxic and hemotoxic bitter colorless liquid containing proteins, which may produce local inflammation. It may have similarities to sea nettle toxin.

Barbiturate overdose

Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe (respiratory depression). Complications of overdose can include noncardiogenic pulmonary edema. If death occurs this is typically due to a lack of breathing.Barbiturate overdose may occur by accident or purposefully in an attempt to cause death. The toxic effects are additive to those of alcohol and benzodiazepines. The lethal dose varies with a person's tolerance and how the drug is taken. The effects of barbiturates occur via the GABA neurotransmitter. Exposure may be verified by testing the urine or blood.Treatment involves supporting a person's breathing and blood pressure. While there is no antidote, activated charcoal may be useful. Multiple doses of charcoal may be required. Hemodialysis may occasionally be considered. Urine alkalinisation has not been found to be useful. While once a common cause of overdose, barbiturates are now a rare cause.

Bee sting

A bee sting is a sting from a bee (honey bee, bumblebee, sweat bee, etc.). The stings of most of these species can be quite painful, and are therefore keenly avoided by many people.

Bee stings differ from insect bites, and the venom or toxin of stinging insects is quite different. Therefore, the body's reaction to a bee sting may differ significantly from one species to another. In particular, bee stings are acidic, whereas wasp stings are alkaline, so the body's reaction to a bee sting may be very different from that of a wasp sting.The most aggressive stinging insects are vespid wasps (including bald-faced hornets and other yellowjackets) and hornets (especially the Asian giant hornet). All of these insects aggressively defend their nests.

Although for most people a bee sting is painful but otherwise relatively harmless, in people with insect sting allergy, stings may trigger a dangerous anaphylactic reaction that is potentially deadly. Additionally, honey bee stings release pheromones that prompt other nearby bees to attack.


Cinchonism or quinism is a pathological condition caused by an overdose of quinine or quinidine, or their natural source, cinchona bark. Quinine and its derivatives are used medically to treat malaria. In much smaller amounts, quinine is an ingredient of tonic drinks, acting as a bittering agent. Cinchonism can occur from therapeutic doses of quinine, either from one or several large doses. Quinidine (Class 1A anti-arrhythmic) can also cause cinchonism symptoms to develop with as little as a single dose.

Diarrhetic shellfish poisoning

Diarrhetic shellfish poisoning (DSP) is one of the four recognized symptom types of shellfish poisoning, the others being paralytic shellfish poisoning, neurotoxic shellfish poisoning and amnesic shellfish poisoning.

As the name suggests, this syndrome manifests itself as intense diarrhea and severe abdominal pains. Nausea and vomiting may sometimes occur too.

DSP and its symptoms usually set in within about half an hour of ingesting infected shellfish, and last for about one day. A recent case in France, though, with 20 people consuming oysters manifested itself after 36 hours. The causative poison is okadaic acid, which inhibits intestinal cellular de-phosphorylation. This causes the cells to become very permeable to water and causes profuse, intense diarrhea with a high risk of dehydration. As no life-threatening symptoms generally emerge from this, no fatalities from DSP have ever been recorded.


Horrilysin (EC, Crotalus horridus metalloendopeptidase, hemorrhagic proteinase IV, Crotalus horridus horridus venom hemorrhagic proteinase) is an enzyme. This enzyme catalyses the following chemical reaction

Cleavage of only the single bond Ala14-Leu in the insulin B chain, Ser12-Leu in the A chain, and Ile-Gly, Pro-Ala, and Ser-Trp in melittinThis endopeptidase is present in the venom of the timber rattlesnake (Crotalus horridus horridus)

Lewis lung carcinoma

Lewis lung carcinoma is a tumor that spontaneously developed as an epidermoid carcinoma in the lung of a C57BL mouse. It was discovered in 1951 by Dr. Margaret Lewis of the Wistar Institute and became one of the first transplantable tumors.


Mastoparan is a peptide toxin from wasp venom. It has the chemical structure Ile-Asn-Leu-Lys-Ala-Leu-Ala-Ala-Leu-Ala-Lys-Lys-Ile-Leu-NH2.The net effect of mastoparan's mode of action depends on cell type, but seemingly always involves exocytosis. In mast cells, this takes the form of histamine secretion, while in platelets and chromaffin cells release serotonin and catecholamines are found, respectively. Mastoparan activity in the anterior pituitary gland leads to prolactin release.

In the case of histamine secretion, the effect of mastoparan takes place via its interference with G protein activity. By stimulating the GTPase activity of certain subunits, mastoparan shortens the lifespan of active G protein. At the same time, it promotes dissociation of any bound GDP from the protein, enhancing GTP binding. In effect, the GTP turnover of G proteins is greatly increased by mastoparan. These properties of the toxin follow from the fact that it structurally resembles activated G protein receptors when placed in a phospholipid environment. The resultant G protein-mediated signaling cascade leads to intracellular IP3 release and the resultant influx of Ca2+.

Research has shown that Mastoparan inhibits all developmental forms of Trypanosoma cruzi, the parasite that is responsible for Chagas disease.

Neurotoxic shellfish poisoning

Neurotoxic shellfish poisoning is caused by the consumption of shellfish contaminated by breve-toxins or brevetoxin analogs.Symptoms in humans include vomiting and nausea and a variety of neurological symptoms such as slurred speech. No fatalities have been reported but there are a number of cases which led to hospitalization.

Opisthacanthus capensis

Opisthacanthus capensis (Thorell, 1876) is a Cape Province and Zimbabwean species of scorpion with robust chelae, dark brown to black in colour, turning green when under cover for some time. Opisthacanthus is arboreal and ground-dwelling, and found mainly in moist habitats in dense vegetation, pine plantations and forests, hiding under bark and rocks. There are 32 species and subspecies in this genus, all occurring in Southern Africa.Its venom contains powerful neurotoxins and cytotoxins, including mucopolysaccharides, hyaluronidases, phospholipases, serotonins, histamines, enzyme inhibitors, and proteins such as neurotoxic peptides. The venom from O. capensis is largely composed of melittin which stimulates the release of the enzyme phospholipase A2 causing inflammation and pain. Phospholipase A2 cleaves the SN-2 acyl chain, releasing arachidonic acid.

This species features in the diets of the bat-eared fox Otocyon megalotis (Canidae), the yellow mongoose Cynictis penicillata, the small grey mongoose Galerella pulverulenta, and the water mongoose Atilax paludinosus (Viverridae).

Paralytic shellfish poisoning

Paralytic shellfish poisoning (PSP) is one of the four recognized syndromes of shellfish poisoning, which share some common features and are primarily associated with bivalve mollusks (such as mussels, clams, oysters and scallops). These shellfish are filter feeders and accumulate neurotoxins, chiefly saxitoxin, produced by microscopic algae, such as dinoflagellates, diatoms, and cyanobacteria. Dinoflagellates of the genus Alexandrium are the most numerous and widespread saxitoxin producers and are responsible for PSP blooms in subarctic, temperate, and tropical locations. The majority of toxic blooms have been caused by the morphospecies Alexandrium catenella, Alexandrium tamarense, Gonyaulax catenella and Alexandrium fundyense, which together comprise the A. tamarense species complex. In Asia, PSP is mostly associated with the occurrence of the species Pyrodinium bahamense.Also some pufferfish, including the chamaeleon puffer, contain saxitoxin, making their consumption hazardous.


Pardaxin is a peptide produced by the Red Sea sole (P4, P5) and the Pacific Peacock sole (P1, P2, P3) that is used as a shark repellent. It causes lysis of mammalian and bacterial cells, similar to melittin.

Phospholipase A2

Phospholipases A2 (PLA2s) EC are enzymes that cleave fatty acid in position two of phospholipids, hydrolyzing the bond between the second fatty acid “tail” and the glycerol molecule. This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond, releasing arachidonic acid and lysophosphatidic acid. Upon downstream modification by cyclooxygenases or lipoxygenases, arachidonic acid is modified into active compounds called eicosanoids. Eicosanoids include prostaglandins and leukotrienes, which are categorized as anti-inflammatory and inflammatory mediators.PLA2 enzymes are commonly found in mammalian tissues as well as arachnid, insect, and snake venom. Venom from both snakes and insects is largely composed of melittin, which is a stimulant of PLA2. Due to the increased presence and activity of PLA2 resulting from a snake or insect bite, arachidonic acid is released from the phospholipid membrane disproportionately. As a result, inflammation and pain occur at the site. There are also prokaryotic A2 phospholipases.

Additional types of phospholipases include phospholipase A1, phospholipase B, phospholipase C, and phospholipase D.

Schmidt sting pain index

The Schmidt sting pain index is a pain scale rating the relative pain caused by different hymenopteran stings. It is mainly the work of Justin O. Schmidt (born 1947), an entomologist at the Carl Hayden Bee Research Center in Arizona. Schmidt has published a number of papers on the subject, and claims to have been stung by the majority of stinging Hymenoptera.

His original paper in 1983 was a way to systematize and compare the hemolytic properties of insect venoms. The index contained in the paper started from 0 for stings that are completely ineffective against humans, progressed through 2, a familiar pain such as a common bee or wasp sting and finished at 4 for the most painful stings. Synoeca septentrionalis, along with other wasps in the genus Synoeca, bullet ants and tarantula hawks were the only species to attain this ranking. In the conclusion, some descriptions of the most painful examples were given, e.g.: "Paraponera clavata stings induced immediate, excruciating pain and numbness to pencil-point pressure, as well as trembling in the form of a totally uncontrollable urge to shake the affected part."

Subsequently, Schmidt has refined his scale, culminating in a paper published in 1990, which classifies the stings of 78 species and 41 genera of Hymenoptera. Schmidt described some of the experiences in vivid detail.An entry in The Straight Dope reported that "implausibly exact numbers" which do not appear in any of Schmidt’s published scientific papers were "wheedled out of him" by Outside magazine for an article it published in 1996.In September 2015, Schmidt was co-awarded the Ig Nobel Physiology and Entomology prize with Michael Smith, for their Hymenoptera research.

Shellfish poisoning

Shellfish poisoning includes four syndromes that share some common features and are primarily associated with bivalve molluscs (such as mussels, clams, oysters and scallops.) As filter feeders, these shellfish may accumulate toxins produced by microscopic algae, such as cyanobacteria, diatoms and dinoflagellates.

Sulfuric acid poisoning

Sulfuric acid poisoning refers to ingestion of sulfuric acid, found in lead-acid batteries and some metal cleaners, pool cleaners, drain cleaners and anti-rust products.

Tin poisoning

Tin poisoning refers to the toxic effects of tin and its compounds. Cases of poisoning from tin metal, its oxides, and its salts are "almost unknown"; on the other hand certain organotin compounds are almost as toxic as cyanide.

William DeGrado

William F. "Bill" DeGrado, Ph.D., is the Professor of Pharmaceutical Chemistry at the University of California, San Francisco (UCSF) and a member of the National Academy of Sciences.

He received a B.S. (chemistry) from Kalamazoo College and a Ph.D. (Chemistry) from the University of Chicago in 1977 working with Emil T. Kaiser and F. Kezdy. His graduate work focused on the design of the oxime resin for solid-phase synthesis, which was used for synthesis of protected peptides and is still in use for various types of combinatorial chemistry today. He also used peptide design to demonstrate that melittin adopts an amphiphilic helical structure, which is responsible for its membrane-disrupting activity.

He first held an industrial position at DuPont Central Research & Development (later DuPont Merck Pharmaceutical Company). He transitioned to academia in 1996, joining the University of Pennsylvania as the George W. Raiziss professor of biochemistry and biophysics and then moved to UCSF in 2011.

His published research includes contributions to the fields of protein design, synthesis of peptidomimetics, and characterization of membrane-active peptides and proteins, most notably the M2 protein.

The M2 proton channel from Influenza A virus. DeGrado’s early work with the groups of Robert Lamb and Larry Pinto established the overall structure and mechanism of the M2 proton channel, which is the target of the anti-influenza drugs, amantadine and rimantadine. A decade later their crystallographic, and NMR structures defined the fine details of the binding site for these drugs and explained the mechanism of the growing problem of amantadine-resistance. With Michael Klein, Robert Lamb and Larry Pinto, DeGrado extensively characterized the physiological properties of many drug-resistant mutants of the channel, identified those most likely to lead to resistance, and designed new drugs to address the problem of drug-resistant forms of influenza A virus.

Available protein structures:
Pfam  structures / ECOD  
PDBsumstructure summary
Membrane-spanning 4A
Pulmonary surfactant
Antimicrobial cationic peptides
Other, human
Other, nonhuman


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