{PDOC00248}
{PS00275; SHIGA_RICIN}
{BEGIN}
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* Shiga/ricin ribosomal inactivating toxins active site signature *
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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-[SAGV]-[STAL]-R-[FY]-[RKNQST]-
                    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: December 2004 / Pattern and text revised.

[ 1] Endo Y., Tsurugi K., Yutsudo T., Takeda Y., Ogasawara T., Igarashi K.
     "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(1988).
     PubMed=3276522
[ 2] May M.J., Hartley M.R., Roberts L.M., Krieg P.A., Osborn R.W., Lord J.M.
     "Ribosome inactivation by ricin A chain: a sensitive method to assess
     the activity of wild-type and mutant polypeptides."
     EMBO J. 8:301-308(1989).
     PubMed=2714255
[ 3] Funatsu G., Islam M.R., Minami Y., Sung-Sil K., Kimura M.
     "Conserved amino acid residues in ribosome-inactivating proteins from
     plants."
     Biochimie 73:1157-1161(1991).
     PubMed=1742358
[ 4] Strockbine N.A., Jackson M.P., Sung L.M., Holmes R.K., O'Brien A.D.
     "Cloning and sequencing of the genes for Shiga toxin from Shigella
     dysenteriae type 1."
     J. Bacteriol. 170:1116-1122(1988).
     PubMed=2830229
[ 5] Calderwood S.B., Auclair F., Donohue-Rolfe A., Keusch G.T.,
     Mekalanos J.J.
     "Nucleotide sequence of the Shiga-like toxin genes of Escherichia
     coli."
     Proc. Natl. Acad. Sci. U.S.A. 84:4364-4368(1987).
     PubMed=3299365
[ 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.
     "Ribosome-inactivating proteins from plants."
     Biochim. Biophys. Acta 1154:237-282(1993).
     PubMed=8280743
[ 8] Hovde C.J., Calderwood S.B., Mekalanos J.J., Collier R.J.
     "Evidence that glutamic acid 167 is an active-site residue of
     Shiga-like toxin I."
     Proc. Natl. Acad. Sci. U.S.A. 85:2568-2572(1988).
     PubMed=3357883
[ 9] Monzingo A.F., Collins E.J., Ernst S.R., Irvin J.D., Robertus J.D.
     "The 2.5 A structure of pokeweed antiviral protein."
     J. Mol. Biol. 233:705-715(1993).
     PubMed=8411176

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