Question

RNase A is a digestive enzyme seceted by the pancreas into the small intestine, where it hydrolyzes RNA into its component nucleotides. The optimum pH for Rnase A is about 6, and the pK values of the two histidines that serve as catlytic residues are 5.4 and 6.4 the first step of the mechanism is shown.

A. Does ribonuclease proceed via acid-base cataylsis, covalent catalysis, metal ion catalysis, or some combination of these strategies? Explain.

B. Assign the Appropraite pK values to His 12 and His 119.

C.explain why the pH optimum of ribonuclease is pH 6.

Please answer all parts to this question fully with an explanation! Thank you!

Answer 1

A. Ribonuclease proceeds via acid base catalysis. Histidine 12 acts as a base and it receives hydrogen ion from the nucleotide while histidine 119 acts as an acid and is proton donor.

B. The pK value of histidine 12 is 5.4 (actually 5.8) and pK value of histidine 119 is 6.4 (actually 6.2).

C. Histidine 12 and 119 are the main amino acids that take part in the reaction mechanism of the enzyme. But other amino acids like lysine at 41 position and aspartate at 121 position, present in active sites of the enzyme, also play an important role in the intermediate stabilization of histidine of the enzyme with the nucleotide. Considering the pK values of all these amino acids, the enzyme works best at pH value of 6. At this pH value, all of the amino acids are in appropriate charged state as is required for the function of the enzyme.