InterPro domain: IPR001574

A number of bacterial and plant toxins act by inhibiting protein synthesis in eukaryotic cells. The toxins of the shiga and ricin family inactivate 60S ribosomal subunits by an N-glycosidic cleavage which releases a specific adenine base from the sugar-phosphate backbone of 28S rRNA [ 1 , 2 , 3 ]. Members of the family include shiga and shiga-like toxins, and type I (e.g. trichosanthin and luffin) and type II (e.g. ricin, agglutinin and abrin) ribosome inactivating proteins (RIPs). All these toxins are structurally related. RIPs have been of considerable interest because of their potential use, conjugated with monoclonal antibodies, as immunotoxins to treat cancers. Further, trichosanthin has been shown to have potent activity against HIV-1-infected T cells and macrophages [ 4 ]. Elucidation of the structure-function relationships of RIPs has therefore become a major research effort. It is now known that RIPs are structurally related. A conserved glutamic residue has been implicated in the catalytic mechanism [ 5 ]; this lies near a conserved arginine, which also plays a role in catalysis [ 6 ].

1. Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of Shiga toxin on eukaryotic ribosomes. RNA N-glycosidase activity of the toxins. Eur. J. Biochem. 171, 45-50
2. Ribosome inactivation by ricin A chain: a sensitive method to assess the activity of wild-type and mutant polypeptides. EMBO J. 8, 301-8
3. Conserved amino acid residues in ribosome-inactivating proteins from plants. Biochimie 73, 1157-61
4. Structure of trichosanthin at 1.88 A resolution. Proteins 19, 4-13
5. Evidence that glutamic acid 167 is an active-site residue of Shiga-like toxin I. Proc. Natl. Acad. Sci. U.S.A. 85, 2568-72
6. The 2.5 A structure of pokeweed antiviral protein. J. Mol. Biol. 233, 705-15