Bovine Pancreatic Ribonuclease A (RNase A) is a small enzyme which catalyzes the degradation of RNA in two steps - transphosphorylation to form a 2',3'-cyclic nucleotide followed by hydrolysis to form a 3'-nucleotide. Several mechanisms have been proposed in the literature involving His12 and His119 as general base and acid, respectively. Herein we present simulation results for each stage along the reaction path to give insight into the involvement, orientation and protonation states of the active site residues of RNase A. The results suggest that the flipped orientation of His12 acts as the general base and Lys41 stabilizes the activated precursor and transition state analog.  Study of RNase A, as the protein analog of other archetype self-cleaving RNA enzymes, provides insight into the different catalytic strategies taken by enzymes and ribozymes to achieve biological function.

Molecular simulations of the catalytic mechanism of RNase A: Comparison of catalytic strategies of enzymes and ribozymes

245th National Meeting (2013)

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