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Multiple Choice
An enzyme has two key catalytic residues, Glu 35 (pKa= 5.9) and Asp 52 (pKa= 4.5). Which of the following is likely true about the mechanism for this enzyme if the optimum pH = 5.2?
A
Glu 35 is more likely a nucleophile than Asp 52.
B
Glu 35 is more likely a general acid than Asp 52.
C
Both a and b are true.
D
a, b & c are false.
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Verified step by step guidance
1
Understand the role of pKa in enzyme catalysis: The pKa value of an amino acid residue in an enzyme indicates the pH at which the residue is half ionized. This is crucial for determining whether a residue acts as a nucleophile or a general acid/base in the enzyme's mechanism.
Consider the optimum pH: The enzyme's optimum pH is 5.2, which is between the pKa values of Glu 35 (5.9) and Asp 52 (4.5). At this pH, Glu 35 is more likely to be protonated, while Asp 52 is more likely to be deprotonated.
Evaluate the nucleophilic potential: A nucleophile is typically deprotonated and negatively charged, making it more reactive. Since Asp 52 has a lower pKa and is more likely deprotonated at pH 5.2, it is more likely to act as a nucleophile than Glu 35.
Assess the general acid potential: A general acid donates a proton during catalysis. Glu 35, with a higher pKa, is more likely to be protonated at pH 5.2, making it more suitable to act as a general acid compared to Asp 52.
Conclude based on the analysis: Given the pKa values and the optimum pH, Glu 35 is more likely to act as a general acid, while Asp 52 is more likely to act as a nucleophile. Therefore, the statement 'Glu 35 is more likely a general acid than Asp 52' is true.