CAalpha-CAbeta-CAgamma: The acidic subunit of crotoxin (CA) is a heterotrimer of three disulfide-linked chains generated by post-translational maturation of a PLA2-like precursor. CA has no PLA2 activity and is not neurotoxic by itself, but plays several important functions in the crotoxin complex by increasing the lethal potency of the uncomplexed CB subunit. It acts by physically occluding the hydrophobic interfacial binding surface (IBS) of CB (PubMed:21787789 and PubMed:21787789). This effect decreases the adsorption of CB to phospholipid membranes, targeting the crotoxin complex to reach the specific presynaptic receptor (R48) at the neuromuscular junction. It also prevents the formation of the reactive CB dimer. Moreover, the CA subunit inhibits the catalytic activity by partially masking the catalytic site of CB (PubMed:21787789) and inhibits its anticoagulant activity. Heterodimer CA-CB: Crotoxin is a potent presynaptic neurotoxin that possesses phospholipase A2 (PLA2) activity and exerts a lethal action by blocking neuromuscular transmission. It consists of a non-covalent association of a basic and weakly toxic PLA2 subunit (CBa2, CBb, CBc, or CBd), with a small acidic, non-enzymatic and non-toxic subunit (CA1, CA2, CA3 or CA4). The complex acts by binding to a specific 48-kDa protein (R48/CAPT) receptor located on presynaptic membranes, forming a transient ternary complex CA-CB-R48, followed by dissociation of the CA-CB complex and release of the CA subunit (PubMed:12657321). At equilibrium, only the CB subunits remain associated with the specific crotoxin receptor. In addition to neurotoxicity, crotoxin has been found to exert myotoxicity, nephrotoxicity, and cardiovascular toxicity (PubMed:20109480). Moreover, anti-inflammatory, immunomodulatory, anti-tumor and analgesic effects of crotoxin have also been reported (PubMed:20109480). Found in the venom as a monomer and stabilized by one disulfide bond (Cys-131 and Cys-138) (PubMed:18495297). This peptide induces potent antinociceptive effects in acute and chronic pain models (PubMed:18495297, PubMed:18703042). This effect is mediated by the release of peripheral dynorphin A, an endogenous agonist of kappa-opioid receptors, and this release is dependent on cannabinoid receptor CB2 activation (PubMed:24460677). Heterodimer of one of the acidic (CA1, CA2, CA3 or CA4) and one of the basic (CBa1, CBa2, CBb, CBc or CBd) subunits; non-covalently linked. The acidic subunit is non-toxic, without enzymatic activity and comprises 3 peptides that are cross-linked by 5 disulfide bridges. The basic subunit is toxic, has phospholipase A2 activity and is composed of a single chain. Multiple variants of each subunit give different crotoxin complexes that can be subdivided into 2 classes: (1) those of high toxicity, low PLA2 activity (CBb, CBc and CBd linked with high affinity to any CA) and high stability (K(d)=4.5 nM) and (2) those of moderate toxicity, high PLA2 activity (CBa2 linked with low affinity to any CA) and low stability (K(d)=25 nM). Expressed by the venom gland. Monoisotopic mass. In class 2 heterodimer CA2-CBa2, LD(50) is 420 ug/kg by intravenous injection into mice. In class 2 heterodimer CA2-CBa2, LD(50) is 650 ug/kg by subcutaneous injection into mice. In class 2 heterodimer CA3-CBa2, LD(50) is 450 ug/kg by intravenous injection into mice. In class 1 heterodimer CA2-CBb, LD(50) is 110 ug/kg by intravenous injection into mice. In class 1 heterodimer CA3-CBb, LD(50) is 95 ug/kg by intravenous injection into mice. In class 1 heterodimer CA2-CBc, LD(50) is 80 ug/kg by intravenous injection into mice. In class 1 heterodimer CA3-CBc, LD(50) is 110 ug/kg by intravenous injection into mice. In class 1 heterodimer CA2-CBd, LD(50) is 70 ug/kg by intravenous injection into mice. In class 1 heterodimer CA2-CBd, LD(50) is 150 ug/kg by subcutaneous injection into mice. In class 1 heterodimer CA3-CBd, LD(50) is 90 ug/kg by intravenous injection into mice. Crotoxin (CA-CBc) is under phase II clinical trial as an anti-tumor drug. The crotoxin heterodimer is inhibited by the crotoxin inhibitor from Crotalus serum (CICS). CICS neutralizes the lethal potency of crotoxin and inhibits its PLA2 activity. CICS only binds tightly to the CB subunit and induces the dissociation of the heterodimer (By similarity). Tested on the CA2-CBd heterodimer (PubMed:10903514). Belongs to the phospholipase A2 family. Group II subfamily. D49 sub-subfamily.