SELF-INHIBITION OF N-GLYCOSIDASE ACTIVITY OF SHIGA TOXIN

Shiga toxin specifically inhibits protein synthesis in eukaryotic cell s; it consists of an enzymatically active A subunit, which is a 28S-rR NA-specific N-glycosidase, and five B subunits. X-Ray data suggest tha t the active center of shiga toxin is partly blocked by the C-terminal part of the A subunit. We demonstrate that physical separation of the active center from the contacting region of the A chain by means of s ite-directed mutagenesis and chemical modification increases the N-gly cosidase activity about 50-fold in a cell-free system. We consider how the polypeptide chains of shiga toxin interact to maintain the mechan ism of self-inhibition.