Ricin structure

Lord, J.M., Roberts, L.M., Robertus, J.D. (1994). Ricin structure, mode of action, and some current applications. FASEB J. 8 201-8. 

Olsnes S (1976). Abrin and ricin structure and mechanism of action of two toxic lectins. Bull Inst Pasteur, 74, 85-99. 

Lord J M, Roberts L M, Robertus J D (1994). Ricin Structure, mode of action and some cnrrent applications. FASEB I. 8(2) 201-208. 

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. 

As in the case of MBS, discussed previously, SMPB was found to be more effective than aliphatic crosslinkers in producing immunotoxin conjugates with ricin that have high yields of cytotoxicity (Myers et al., 1989). This was attributed to the reagent s aromatic ring structure. A comparison with SPDP produced immunotoxin conjugates concluded that SMPB formed more stable complexes that survive in serum for longer periods (Martin and Papahadjopoulos, 1982). 

Fig. 3 Secondary structure of the ribosomal rRNA of Saccharomyces cerevisiae. http //www.ma.icmb.utexas. edu (Cannone et al. 2002). The numbering of nucleotides is according to E. coli. Helices H) discussed in the text are highlighted and localization of yeast rdn mutations are indicated, a Secondary structure of the small subunit 18S rRNA. Helices discussed in the text are labeled in red. b Secondary structure of the 25 rRNA. Helices discussed in the text are labeled in blue. Helix 44 is part of the L7/L12 stalk hehx 95 contains the sarcin-ricin loop. For details, see text...

Nicotinic acid undoubtedly provides the basic skeleton for some other alkaloids. Ricinine (Figure 6.35) is a 2-pyridone structure and contains a nitrile grouping, probably formed by dehydration of a nicotinamide derivative. This alkaloid is a toxic constituent of castor oil seeds (Ricinus communis Euphorbiaceae), though the toxicity of the seeds results mainly from the polypeptide ricin (see page 434). Arecoline (Figure 6.36) is found in Betel nuts (Areca catechu Palmae/Arecaceae) and is a tetrahydronicotinic acid derivative. Betel nuts are chewed in India and Asia for the stimulant effect of arecoline. 

Specific metal ion binding sites are directly observed in the crystal structures of hammerhead ribozymes [18], P4—P6 domain of Tetrahymena group I intron [19], transfer (tRNA) [20], GAAA tetraloop receptor [21], sarcin-ricin loop [22], and MMTV pseudoknots [23], for example. High... 

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. 

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). 

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