Ricin protein structure

Davis, J.H. (1978). Abrus precatorius (rosary pea). The most common lethal plant poison. J. F/orzWaMerf. Hi i oc. 65 188-91. Day, P.J., Pinheiro, T.J., Roberts, L.M., Lord, J.M. (2002). Binding of ricin A-chain to negatively charged phospholipid vesicles leads to protein structural changes and destabilizes the lipid hilayer. Biochemistry 41 2836-43. 

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). 

Figure 20.9 illustrates a graphical representation of ricin s protein structure found by crystallography [76]. This protein inhibits the function of the ribosome and stops protein synthesis by N-glycosidase enzymatic activity in ribosomal RNA [77]. 

FIGURE 20.9 Protein structure of ricin determined by X-ray crystallography. Source E. Rutenber, et al. (1991) Crystallographic refinement of ricin to 2.5 A. Proteins, 10, 240-250. 

Ricin is extremely toxic to eukaryotic cells.32,150,194,642,844,646,647,649,657 The experiments of Olsnes and Pihl150,639,649 and Pappenheimer and coworkers658 demonstrated that one of the two subunits binds to the cell membrane, presumably by way of a carbohydrate structure, whereas the second subunit inhibits protein synthesis by a catalytic mechanism in a cell-free system. This suggests that toxicity may result from the... 

Radioactive labeling of proteins is very useful for studying the interactions and binding of these molecules to cells, membranes, as well as to molecular structures. For studying such interactions, radioactive ricin can serve as an example... 

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. 

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). 

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... 

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. 

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