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1. Which of the following statements is most FALSE regarding the activity of His

ID: 151484 • Letter: 1

Question

1. Which of the following statements is most FALSE regarding the activity of His12 in RNase A? a.His12 initially acts as a general base removing a proton from the 2'-OH group of the ribose sugar. b. The protonation state of His12 is finally restored by donating a proton to the RNA leaving group c.His12 removes a proton from water, generating a nucleophilic hydroxide group d.His12 does not bind directly to the substrate to form an enzyme-substrate covalent intermediate 2.Due to transition state stabilization, the enzyme proline racemase would be predicted to bind to an intermediate with a tetrahedral carbon at the reaction site rather than a trigonal planar carbon a. True b. False

Explanation / Answer

Ans1 - a

His12 acts as a general base, accepting the 2'-OH proton of the sessile ribonucleic sugar ring.

This promotes a nucleophilic attack by the 2'-O on the more positively-charged phosphorus (P) atom thereby creating a 2’,3’-cyclic ribonucleotide phosphate intermediate. The creation of this intermediate is facilitated by the imidazole of His119 which acts as a general acid, donating its proton to the oxygen atom in the susceptible P-O-R' bond.

Ans2- (b)False

The racemization of L-proline to D-proline proceeds through a planar transition state, where the tetrahedral -carbon becomes trigonal as a proton leaves the L-proline.