RNA N-glycosidase (EC 3.2.2.22) (RIP)

RNA N-glycosidases (EC 3.2.2.22) are a class of enzymes, primarily known as Ribosome-Inactivating Proteins (RIPs), that catalyze the site-specific depurination of the sarcin/ricin loop (SRL) in the large ribosomal subunit (UniProt: P02879). By removing a single adenine residue (A4324 in rat, A4323 in human) from the 28S rRNA, these enzymes irreversibly damage the ribosome, preventing the binding of elongation factors EF-1 and EF-2 and effectively halting protein synthesis (PubMed: 11433344). This mechanism is most famously utilized by potent toxins such as Ricin and Shiga toxin, which are produced by plants and bacteria, respectively (PubChem: CID 3081340). In a clinical context, RNA N-glycosidases are significant both as threats—such as in Shiga-toxigenic E. coli infections—and as therapeutic tools. They are frequently engineered into immunotoxins, where the catalytic domain is conjugated to a targeting moiety like a monoclonal antibody to selectively kill cancer cells (PubMed: 25133834). Research into small-molecule inhibitors, such as Retro-2, is ongoing to develop treatments for toxin exposure and associated complications like Hemolytic Uremic Syndrome (PubMed: 20448183). These enzymes are also studied for their potential in antiviral and antifungal applications due to their ability to disrupt the translational machinery of pathogens. Therapeutic challenges include the extreme systemic toxicity of these proteins and the risk of vascular leak syndrome when used in immunotoxin therapy (PubMed: 11877304).

Other names

rRNA N-glycosylaseRibosome-inactivating proteinType I RIPType II RIPSaporinRicinShiga toxinAbrinGelonin

Catalyzes the hydrolytic cleavage of the N-glycosidic bond of a specific adenine residue within the sarcin/ricin loop of the large ribosomal subunit, preventing elongation factor binding (PubMed: 11433344).