Question

If histidine (pKa=6.04) is the nucleophile in an enzyme participating in covalent catalysis at pH=5, what would be most advantageous in the vicinity of the active site histidine?

a) Glutamate (pKa=4.0)
b) Aspartate (pKa=3.9)
c) Lysine (pKa=10.5)
d) Arginine (pKa=12.5)

Answer 1

The most advantageous amino acid to have in the vicinity of the active site histidine for covalent catalysis at pH 5 would be Aspartate (pKa=3.9).

Step-by-step explanation:

The most advantageous amino acid to have in the vicinity of the active site histidine for covalent catalysis at pH 5 would be Aspartate (pKa=3.9).

Aspartate has a lower pKa value than histidine, which means it is more likely to be protonated and have a negative charge at pH 5. This negatively charged aspartate can stabilize the positive charge on the histidine, enhancing its ability to act as a nucleophile in covalent catalysis.

In contrast, glutamate (pKa=4.0), lysine (pKa=10.5), and arginine (pKa=12.5) would all have higher pKa values than histidine at pH 5, and therefore would not be beneficial for stabilizing the histidine's positive charge.