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- *******************************************************************
- * Shiga/ricin ribosomal inactivating toxins active site signature *
- *******************************************************************
-
- 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]. The toxins
- which are known to function in this manner are:
-
- - Shiga toxin from Shigella dysenteriae [4]. This toxin is composed of one
- copy of an enzymatically active A subunit and five copies of a B subunit
- responsible for binding the toxin complex to specific receptors on the
- target cell surface.
- - Shiga-like toxins (SLT) are a group of Escherichia coli toxins very
- similar in their structure and properties to Shiga toxin. The sequence of
- two types of these toxins, SLT-1 [5] and SLT-2 [6], is known.
- - Ricin, a potent toxin from castor bean seeds. Ricin consists of two
- glycosylated chains linked by a disulfide bond. The A chain is
- enzymatically active. The B chain is a lectin with a binding preference for
- galactosides. Both chains are encoded by a single polypeptidic precursor.
- Ricin is classified as a type-II ribosome-inactivating protein (RIP); other
- members of this family are agglutinin, also from castor bean, and abrin
- from the seeds of the bean Abrus precatorius [7].
- - Single chain ribosome-inactivating proteins (type-I RIP) from plants.
- Examples of such proteins are: barley protein synthesis inhibitors I and
- II, mongolian snake-gourd trichosanthin, sponge gourd luffin-A and -B,
- garden four-o'clock MAP, common pokeberry PAP-S and soapwort saporin-6 [7].
-
- All these toxins are structurally related. A conserved glutamic residue has
- been implicated [8] in the catalytic mechanism; it is located near a conserved
- arginine which also plays a role in catalysis [9]. The signature we developed
- for these proteins includes these catalytic residues.
-
- -Consensus pattern: [LIVMA]-x-[LIVMSTA](2)-x-E-[AGV]-[STAL]-R-[FY]-[RKNQS]-x-
- [LIVM]-[EQS]-x(2)-[LIVMF]
- [E and R are active site residues]
- -Sequences known to belong to this class detected by the pattern: ALL.
- -Other sequence(s) detected in SWISS-PROT: NONE.
- -Last update: June 1994 / Text revised.
-
- [ 1] Endo Y., Tsurugi K., Takeda Y., Ogasawara T., Igarashi K.
- Eur. J. Biochem. 171:45-50(1988).
- [ 2] May M.J., Hartley M.R., Roberts L.M., Krieg P.A., Osborn R.W., Lord J.M.
- EMBO J. 8:301-308(1989).
- [ 3] Funatsu G., Islam M.R., Minami Y., Sung-Sil K., Kimura M.
- Biochimie 73:1157-1161(1991).
- [ 4] Strockbine N.A., Jackson M.P., Sung L.M., Holmes R.K., O'Brien A.D.
- J. Bacteriol. 170:1116-1122(1988).
- [ 5] Calderwood S.B., Auclair F., Donohue-Rolfe A., Keusch G.T.,
- Mekalanos J.J.
- Proc. Natl. Acad. Sci. U.S.A. 84:4364-4368(1987).
- [ 6] Jackson M.P., Neill R.J., O'Brien A.D., Holmes R.K., Newland J.W.
- FEMS Microbiol. Lett. 44:109-114(1987).
- [ 7] Barbieri L., Battelli M.G., Stirpe F.
- Biochim. Biophys. Acta 1154:237-282(1993).
- [ 8] Hovde C.J., Calderwood S.B., Mekalanos J.J., Collier R.J.
- Proc. Natl. Acad. Sci. U.S.A. 85:2568-2572(1988).
- [ 9] Monzingo A.F., Collins E.J., Ernst S.R., Irvin J.D., Robertus J.D.
- J. Mol. Biol. 233:705-715(1993).
-