Antiviral Studies with Trichosanthin, A Plant Derived Single Chain Ribosome Inactivating Protein

Abstract

Ribosome inactivating proteins (RIPs) are a family of plant derived proteins that have the capability to functionally inactivate ribosomes through an enzymatic mechanism (reviewed in 1,2). RIPs can be divided into two classes. Single chain RIPs (SCRIPs) such as trichosanthin consist of a single protein chain with enzymatic activity capable of mediating ribosome inactivation (1,2). Two chain RIPs, or toxins, as typified by ricin and abrin, consist of a B chain that mediates attachment to cell surfaces (through lectin-like binding to specific carbohydrate moieties) and perhaps facilitates translocation through cell membranes. The B chain is covalently linked to an A chain essentially comparable to a SCRIP, that contains ribosome modifying enzyme activity (1,2). Plant derived RIPs are N-glycosidases and depurinate a particular adenine residue in 28S rRNA in a site-specific fashion, resulting in structural modification and functional inactivation of the affected ribosomes, perhaps through impairment of ability to bind elongation factors (3–6).