Non-toxic type 2 ribosome-inactivating proteins (RIPs) from Sambucus: occurrence, cellular and molecular activities and potential uses.
Ribosome-inactivating proteins (RIPs) are a family of enzymes that trigger the catalytic inactivation of ribosomes. The most known member of the family is the highly poisonous two-chain ricin isolated from Ricinus communis L. Sambucus species contain a number of two-chain RIPs structurally and enzymatically related to ricin which have the noteworthy feature that, having an enzymatic activity on ribosomes, leading to the inhibition of protein synthesis, higher than ricin, they are lacking of the tremendous unspecific toxicity of ricin. Therefore, they have been called non-toxic type 2 RIPs. The most representative and studied members are nigrin b present in the bark of the common (black) elder Sambucus nigra L. and ebulin 1 present in the leaves of the dwarf elder Sambucus ebulus L. The molecular basis for the low unspecific activities of nigrin b and ebulin 1 as compared with ricin seems to be related with single changes of amino acids in the high affinity sugar binding sites of the B chains. These changes determine the intracellular traffic of these proteins and thus the cellular toxicity. Conjugation ofnigrin b or ebulin 1 to either transferrin or monoclonal antibodies provided highly active conjugates targeting cancer. Thus these non-toxic type 2 RIPs are promising tools for cancer therapy.
Girbes
T
T
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Valladolid, 47005 Valladolid, Spain. girbes@bio.uva.es
Ferreras
J M
JM
Arias
F J
FJ
Muñoz
R
R
Iglesias
R
R
Jimenez
P
P
Rojo
M A
MA
Arias
Y
Y
Perez
Y
Y
Benitez
J
J
Sanchez
D
D
Gayoso
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism*; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism*; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000378:metabolism; D027923:Sambucus / Q000201:enzymology / Q000378:metabolism*; D013308:Streptonigrin / Q000378:metabolism
D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; C107391:ebulin r protein, Sambucus ebulus; D013308:Streptonigrin; D012276:Ricin; D009699:N-Glycosyl Hydrolases