Ricin toxin structure

Diagram 1. Representation of the ricin toxin subunit structure. The A-subunit is an enzyme and the B-subunit a lectin. The B-subunit plays a crucial role in binding to the cell surface thereby allowing the entry of the A-subunit into the cell. Once inside the cell the A-subunit separates and exerts its toxic effects. 

For example, the P-trefoil fold of CBM13 is classified into the Ricin-B-like family along with a bona //de lectin (ricin toxin B-chain) [57]. CBM42 also has structural similarity to ricin toxin B-chain, binding to small sugar units and displaying multivalency [58]. 

Figure 21.2 illustrates the basic structure of these common two-subunit toxins, showing schematically their major characteristics. The molecular model of ricin is from Rutenber et al. (1991), RSCB structure No. 2aai. 

The toxic ricin is a small protein molecule consisting of two parts, chains A and B. The B chain is similar to proteins called lectins which recognize and bind to the membranes surrounding the cells in our bodies. The B chain attaches the ricin to the cell membrane which then folds inwards so that the ricin molecule is taken inside the cell inside a bag called a vacuole. There is only one bond between the A and B chains and this now breaks. The B chain then makes a hole in the vacuole through which the A chain passes into the cell. Here it heads straight for structures called ribosomes, where proteins, many of which are vital for the functioning of our bodies, are made. The A chain then selectively removes a specific molecule (the base adenine) from the RNA in the ribosomes. RNA contains the information required to make proteins, and removal of part of the information blocks the synthesis of proteins. The cell therefore dies. One molecule of ricin may be sufficient to kill one cell. This makes it the most potent toxin known. 

CWAs are represented by any one of a number of chemicals exhibiting a very high toxicity by various mechanisms. The present Handbook exhibits CWAs with structures as simple as carbon monoxide (CO) and as complex as botulinum toxin or ricin proteins. While this chapter could address the development of PBPK models of CWAs in general, the focus will primarily be on the organophosphate (OP)-based nerve agents typically represented by sarin (GB - isopropyl methylfluoro-phosphonate). 

Diphtheria toxin is produced as a single polypeptide chain (Fig. la) yyhich is easily cleaved ("nicked") by trypsin and trypsin-like proteases into two disulfide-linked fragments, A and B (Pappenheimer, 1977). The structure of the nicked toxin resembles that of the plant toxins ricin, abrin, modeccin, viscumin and others (Olsnes and Sandvig, 1985). 

Chemical Abstracts Service Registry Number CAS 1393-62-0. Abrin is a toxalbumin similar in structure, absorption, and mechanism of action to ricin but is found not in castor beans but rather in jequirity beans. No reports of its use as a battlefield or terrorist agent exist, but in mice it is 75 times more potent than ricin. No specific treatment is available. Both ricin and abrin are type 2 ribosomal inhibitory proteins (RIPs) the other potent toxins in this class are Eranthis hyemalis lectin (EHL) from winter aconite, modeccin and volkensin from African succulents, and viscumin from mistletoe. 

Shiga toxin produced by Shigella dysenteriae has similar structural features. The toxin binds to a glycolipid (Gb3), undergoes endocytosis, and the enzymatie Ai fragment, which is a specific N-glycosidase, removes adenine from one particular adenosine residue in the 28S RNA of the 60S ribosomal subunit. Removal of the adenine inactivates the 60S ribosome, blocking protein synthesis. Ricin, abrin, and a number of related plant proteins inhibit eukaryotic protein synthesis in a similar manner (Chapter 25). 

Miller, D.J., Ravikumar, K., Shen, H., Suh, J.K., Kerwin, S.M. and Robertas, J.D. (2002) Structure-based design and characterization of novel platforms for ricin and shiga toxin inhibition. J Med Chem, 45, 90-98. 

The most studied RNA A-glycosidase is ricin, from the castor oil bean, Ricinus communis. This toxin has two component chains, the A chain, containing the A-glycohydrolase, and a B chain which is a lectin (a protein which binds carbohydrate structures, in this case galactopyranose), which facilitates... 

Abrin is a plant toxin, which is closely related to ricin in terms of its structure and chemical properties. It is obtained from the seeds of Abrus pre-catorius (commonly known as jequirity bean or rosary pea ), a tropical vine cultivated as an ornamental plant in many locations. Jequirity beans are usually scarlet in colour with a black spot at one end (though less common different coloured varieties exist) and are approximately 3x8 mm in size. 

Like ricin, abrin is a type 2 ribosome inactivating protein with A and B chains linked by a disulphide bond. The abrin A chain comprises 251 amino acid residues compared to 267 in the ricin A chain, both having three folding structural domains and a molecular weight of approximately 30 kDa. The abrin B chain has a molecular weight of 35 kDa with 60% of its amino acid residues identical to those of ricin s B chain. Both B chains have two saccharide binding sites which are highly conserved between the two toxins. 

---