Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

Ribosome inactivating proteins (RIPs) are a group of glycosylated and non-glycosylated enzymes with N-glycosidase activity that were initially detected in higher plants, but have also been found in fungi, algae and bacteria (for comprehensive reviews, see [201] [202] [203] [204] [205] [206] [207] ). RIPs may be present in one or more tissues of the plant, and their expression is enhanced in senescence and under various stress conditions [208] [209] [210] [211] [212] [213] [214] including microorganisms and viral infections [215] [216] [217] . RIPs are artificially divided into three groups on the basis of their structure and mode of activation: type I RIPs are single chain basic proteins of about 30 kDa with enzymatic activity. Some well known members of this group are saporin (from Saponaria officinalis), pokeweed antiviral protein (PAP) (Phytolacca americana) and gelonin (Gelonium multiforum). Type II RIPs, like ricin (from Ricinus communis) and abrin (Abrus precatorius), are heterodimeric proteins consisting of an enzymatically active A chain of about 30 kDa linked through a disulfide bond to a B chain of approximately 35 kDa which has the properties of a lectin. Type III RIPs, like the maize and the barley proteins b-32 and JIP60, respectively, are synthesized as inactive precursors (proRIPs), which lacks a lectin moiety and are activated by proteolytic processing which includes the removal of terminal sequences and a short inhibitory internal peptide [201, [206] [207] [208] [218] [219] [220] .