Fig. 1.

The concerted general acid/base mechanism for RNase A catalysis. A scheme for active site interactions involving His12, His119 and Lys41 in the ground state, transition state (TSc) and product state are shown from left to right. Note that nucleophilic addition (2’O-P bond formation) and leaving group departure (5’O-P bond cleavage) occur in a single transition state. Proton transfer involving the nucleophile and leaving group occur concomitantly with changes in O-P bonding. General base catalysis involves transfer of the 2’O proton (shown in red) to the deprotonated form of His12. General acid catalysis occurs via transfer of a proton (shown in blue) from the protonated form of His119 to the departing 5’O.