Girbes T, Ferreras J M, Arias F J, Muñoz R, Iglesias R, Jimenez P, Rojo M A, Arias Y, Perez Y, Benitez J, Sanchez D, Gayoso M J
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Valladolid, 47005 Valladolid, Spain.
Cell Mol Biol (Noisy-le-grand). 2003 Jun;49(4):537-45.
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.
核糖体失活蛋白（RIPs）是一类能催化核糖体失活的酶。该家族最著名的成员是从蓖麻中分离出的剧毒双链蓖麻毒素。接骨木属植物含有多种双链RIPs，它们在结构和酶活性上与蓖麻毒素相关，其显著特点是对核糖体具有酶活性，导致蛋白质合成受到抑制，且活性高于蓖麻毒素，同时又缺乏蓖麻毒素那种巨大的非特异性毒性。因此，它们被称为无毒2型RIPs。最具代表性且研究最多的成员是黑接骨木（Sambucus nigra L.）树皮中的黑接骨木蛋白b和矮接骨木（Sambucus ebulus L.）叶片中的欧布ulin 1。与蓖麻毒素相比，黑接骨木蛋白b和欧布ulin 1非特异性活性较低的分子基础似乎与B链高亲和力糖结合位点上的单个氨基酸变化有关。这些变化决定了这些蛋白质在细胞内的运输，进而决定了细胞毒性。将黑接骨木蛋白b或欧布ulin 1与转铁蛋白或单克隆抗体结合可得到靶向癌症的高活性缀合物。因此，这些无毒2型RIPs是很有前景的癌症治疗工具。
