FUNGAL RIBOTOXINS - A FAMILY OF NATURALLY ENGINEERED TARGETED TOXINS

alpha-Sarcin, mitogillin, and restrictocin are small (similar to 17 kD a) basic ribosome-inactivating proteins (RIPs) produced by the Aspergi lli that catalytically inactivate the large ribosomal subunits of all organisms tested to date. These three fungal ribotoxins act as specifi c ribonucleases by hydrolyzing one single phosphodiester bond in the u niversally conserved alpha-sarcin domain of 23-28S rRNAs and are among the most potent inhibitors of protein synthesis known. Previous molec ular studies of ribotoxins indicated that they belong to the superfami ly of ribonucleases and analysis of the mitogillin gene employing PCR- mediated site-specific mutagenesis suggests that certain domains in ri botoxins, which share homologies with motifs in ribosome-related prote ins, may be responsible for the targeting of ribotoxins to the ribosom e. The applications of the ribotoxins as tools in research and their u ses as therapeutic and diagnostic agents are also reviewed in this pap er.