On the mechanism of action of ribonucleases: dinucleotide cleavage catalyzed by imidazole and Zn2+

Abstract

Cyclization/cleavage of the 2-(p-nitrophenyl) phosphate ester of propylene glycol is catalyzed by imidazole and, much more effectively, by Zn2+ with imidazole. In the latter case, the mechanism involves simultaneous Lewis acid/base catalysis. Similar Zn2+ and imidazole catalysis of cyclization/cleavage is seen with the dinucleotide 3',5'-UpU (uridylyluridine). Again, the zinc system is much more effective than is catalysis by imidazole alone, and in this case simultaneous Lewis acid/base catalysis substitutes for the sequential proton acid/base catalysis seen with polynucleotides or dinucleotides and imidazole buffer catalysts. A mechanism is proposed for catalysis of RNA cleavage by the enzyme ribonuclease A, and the relationship of that mechanism to the action of the enzyme model systems is discussed.