Anti-ricin monoclonal antibody, clone MMH

Ricin (RT) is a glycoprotein extracted from castor seeds and is a deadly and highly toxic biotoxin. The molecular weight of ricin is 65KDa. It is a glycoprotein heterodimer composed of two polypeptide chains, A and B. The two chains are connected by disulfide bonds. RTA is a toxic chain with a molecular weight of approximately 32KDa, glycosidase activity, spherical shape, and consists of 267 amino acid residues. RTA has three structural domains, including 8 α-helices, 8 β-turns and some random coils and other conformational structures. The oligosaccharide chain (GlcNac)₂(Man)₄ is connected to the asparagine position of the 10th residue. Glutamic acid at position 177 and arginine at position 180 are located in the active center of the enzyme. Glutamic acid at position 177 is critical to the enzyme. The reaction rate is greatly limited. Arginine at position 180 provides a proton for the substrate adenine, which promotes the cleavage of the N-glycosidic bond. RTB has condensin activity, has a molecular weight of about 34KDa, a dumbbell-shaped structure, and is composed of 262 amino acid residues. RTB has two structural domains, each of which consists of three homologous subdomains: α, β, and γ. RTB has two galactose-binding sites and can bind to galactose-containing glycoproteins or glycolipids on cells. Each subdomain has a potential sugar-binding site, but only the 1α and 2γ substructures can actually bind to sugar. In addition to two galactose binding sites, RTB also has two sugar branch chains (GlcNac)₂(Man)₆ and (GlcNac)₂(Man) ₇. These two branch chains are connected at positions 93 and 133 Asparagine residues respectively, if these two chains are removed, the condensin activity of RTB may be lost.

Figure 1. Intracellular transport of ricin.(Source: Monika Słomińska-Wojewódzka, et al.; 2013)

Purified ricin is a white powder, odorless and tasteless. The white powder of ricin is easily soluble in water and glycerol solutions, soluble in dilute acids and salt aqueous solutions, insoluble in organic solvents such as ether, ethanol, toluene and chloroform, and can be precipitated in saturated ammonium sulfate solutions. Precipitated, ricin is more resistant to heat, acid and alkali than ordinary proteins. There are many types of ricin (crystalline, D-type, E-type, B1-type and T3-type, etc.). The toxicity of different types of ricin is different, among which the D-type protein is the most toxic. Toxins can cause inflammation, gastrointestinal bleeding, tubular necrosis, or hypoglycemia. Ricin can quickly inhibit protein synthesis and may cause cell and tissue damage in a short period of time without obvious symptoms of poisoning. At present, there is a lack of specific drugs against ricin poisoning, so the treatment of ricin poisoning is very difficult. Studies have shown that chicoric acid and rosmarinic acid can inhibit the activity of ricin and are potential therapeutic agents for the treatment of ricin poisoning.

Ricin is a strong cytotoxin, which is a type II glycosome-inactivating protein. Many receptors on the cell surface can bind to it. Most mammalian cells are very sensitive to contact with ricin. Ricinus The toxin is a potential bioterrorist agent and there is currently no effective antidote. Ricin binds to receptors containing galactose residues on the cell surface by relying on the galactose-binding site on RTB, inducing the invagination of ricin molecules to form intracellular vesicles and enter the cells. After the toxin enters the cell, the disulfide bond between RTA and RTB is reduced and cleaved by the Golgi apparatus or lysosome in the cell, releasing the free RTA toxic chain. The main function of RTA is to hydrolyze the adenine N-glycosidic bond at the A4324 position of the 60S large subunit of the eukaryotic ribosome, and remove adenine, causing it to lose RNase resistance. This results in the inability of the 60S large subunit to bind to elongation factor (EF-2) during protein synthesis, interfering with the formation of the complex (GTP) ribosome-EF-2-guanine triphosphate, inhibiting protein synthesis and leading to cell death. Impairment of Induced Cytokine Ricin intoxication causes many symptoms that are incompletely explained by inhibition of protein synthesis. The secretion of tumor necrosis factor (TNF-α) and interleukins (IL-1, IL-6) can affect poisoning phenomena such as fever, ascites, intestinal bleeding, necrotic inflammation, etc. Studies have found that using ricin to stimulate peripheral blood mononuclear cells TNF-α and IL-1 are induced in cells, and a small amount of TNF-α has been detected in the plasma of rats poisoned with ricin. It can be concluded that some symptoms caused by castor poisoning may be related to cytokines. Ricin interacts with macrophages to generate free radicals and reactive oxygen species that cause peroxidative damage to lipids. After ricin was in the body for 36 hours, the lipid peroxidation intensity, DNA single-strand breaks, and reduced glutathione in various organs in the body decreased most strongly. Poisoning is the most serious damage to the liver. It is the main place where exogenous compounds are metabolized in the body and is the organ most susceptible to damage. With the deepening of research, it was found that a certain concentration of ricin can cause cell death by inducing apoptosis. It can not only cause cell death by inhibiting protein translation, but also activate the apoptotic pathway to cause cell apoptosis.

RCA
Ricinus Communis Agglutinin
RCA-II
Ricinus lectin
Castor bean lectin
Ricin toxin
RCA60
RCA120