RNase is an enzyme that cleaves the linkage between the 3' phophate group of one nucleotide and the 5' -OH of
the next nucleotide in the polymer. The mechanism listed below is that of Bovine pancreatic RNase A. The nucleic acid DNA cannot be be degraded by this mechanism because it lacks the 2' hydroxyl group on the ribofuranose subunit.
RNase A (from now on called RNase) relies on the general acid-base catalysis of two Histidine residues. These
are Histidine 12 and Histidine 119.
The Mechanism of RNase
1) In the first step His12 acts as a general base abstracting the hydroxyl proton from the 2' -OH group of the
RNA nucleotide. This primes the 2' hydroxyl oxygen for nucleophilic attack on the phosphate group attached to
the 3' oxygen of the same nucleotide. This nucleophilic attack displaces the 5' oxygen of the next nucleotide
in the polymer. The leaving group (the 5' terminal) is then protonated by His119 acting as a general acid.
This results in a 2'-3' cyclic intermediate. His12 is protonated at the end of this step and His 119 is
unprotonated.
2) In the second step His119 acts as a general base, abstracting a proton from a water molecule. This
promotes the nucleophilic attack of the water onto the 3' phosphate group. This displaces the 2' oxygen that
attacked the phosphate in the previous step. His12 then acts as a general acid by protonating the 2' oxygen
leaving group. This returns the enzyme to its normal state.