Ribonuclease A can be Transformed into a Dimeric Ribonuclease with Antitumor Activity

A cDNA coding for bovine pancreatic RNase A was mutagenized to insert a proline, leucine, and 2 cysteine residues, i.e. the residues present at corresponding positions in the subunit of seminal RNaset, he only dimeric RNase of the pancreatic-type superfamily. The mutant, expressed in Escherichia coli, eventually aggregated into catalytically active dimers. Like naturally dimeric seminal RNase, at equilibrium the mutant dimeric RNase A adopted two quaternary structures (one with an exchange of the N-terminal segments between partner subunitst, he other with no exchange) and displayed a selective toxicity for malignant cells, absent in the monomeric, parent protein.