Newton, D.L., Boque, L., Wlodawer, A., Huang, C.Y. and Rybak, S.M.
Notes: Naturally isolated onconase, a cellular RNase with anti-tumor properties, is not inhibited by the placental ribonuclease inhibitor. The natural protein has a pyroglutamate at the N-terminus as the result of a posttranslational modification starting from an N-terminal methionine followed by a glutamate residue. Recombinant onconase has no activity unless the N-terminal methionine and the glutamate residue is cyclized to form the pyroglutamate moiety. However, conversion of the glutamate to either serine or tyrosine results in RNase activity without processing. This RNase activity is very different from the natural onconase because the Ser and Tyr mutants are inhibited by RNasin® Ribonuclease Inhibitor. Further studies determined that the Tyr and Ser mutants display a 100,000-fold greater sensitivity to the inhibitor that the natural onconase. (1646)