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Question #44979

Difficulty: 8/10 | 🟢 Free

The Question

An enzyme utilizes the imidazole side chain of a Histidine residue ( $\text{p}K_{a1} = 1.8$ , $\text{p}K_{aR} = 6.0$ , $\text{p}K_{a2} = 9.2$ ) as a general base to catalyze the phosphorylation of Guanosine by ATP at $298\text{ K}$ . The reaction specifically targets the most sterically accessible hydroxyl group of the nucleoside's pentose sugar to form a nucleotide. During an in vitro experiment, the reaction buffer is acidified such that the ratio of the protonated to unprotonated imidazole side chain of the catalytic Histidine becomes $100:1$ . At this pH, the catalytic base is effectively 'shut off', and the nucleophilic attack on the phosphate donor is blocked. Identify the target esterification site on Guanosine and the net charge of the predominant Histidine species at this inhibited pH.

Options

A.
5'-OH, +1
B.
3'-OH, 0
C.
5'-OH, +2
D.
2'-OH, +1

Check Your Answer

Correct Answer

Step-by-Step Solution

Explanation

How the Examiner Thinks

Mechanism_Trap

Don't get tricked by the process! Learn the mechanical traps used in competitive exam questions.

Concepts Behind This Question

Nucleoside vs Nucleotide|Amino Acid Zwitterion pH Sensitivity

Why This Question Is Tricky

Common Mistakes

The question tests the student's ability to integrate biochemical structural knowledge (nucleoside regioselectivity) with physical chemistry (pH-dependent amino acid speciation).

The 'Hidden Variable' is the exact calculation of the pH from the given ratio to determine the zwitterionic state.

Students often memorize that Histidine is neutral at physiological pH but fail to systematically calculate its net charge in acidic conditions.

The 'Chemical Exception' trap lies in confusing the alpha-amino group's protonation state with the side chain's protonation state.

A common error is assuming the net charge is +2 by forgetting that the highly acidic carboxyl group (pKa = 1.8) is already deprotonated at pH 4.0.

Another trap is selecting the 3'-OH due to its involvement in phosphodiester bonds during DNA/RNA polymerization, forgetting that initial de novo phosphorylation occurs at the sterically unhindered primary 5'-OH.

Quick Facts About This Question

Question Information

Subject	Chemistry
Chapter	Biomolecules - Class 12
Concept	Nucleoside vs Nucleotide
Difficulty	8
Cognitive Load	7
Target Solve Time	160 sec
Access	Free