Consider a protein in which a negatively charged glutamic acid side chain (pKa = 4.2) makes a salt bridge (ion-ion interaction) with a positively charged histidine side chain (pKa = 6.5).
Part A:
Do you predict that this salt bridge will become stronger, become weaker, or be unaffected as pH increases from pH = 7.2 to pH = 7.8?
The salt bridge will become stronger.
The salt bridge will become weaker.
The salt bridge will be unaffected.
Correct
At pH = 7.2 the glutamic acid (Glu) side chain will carry a charge of ~ -1 (at 3 pH units above the pKa for Glu, the side chain will be almost fully ionized); whereas the histidine (His) side chain will carry a charge of < +0.5 (at pH = pKa the charge on His would be +0.5; since pH = 7.2 is above its pKa, it will carry less (+) charge as it becomes more deprotonated). As the pH increase to 7.8, the charge on Glu will remain ~ -1 and the charge on His will decrease; thus, this salt bridge is predicted to become weaker as pH is raised from 7.2 to 7.8.
Part B:
Justify your answer with calculations of partial charges on these amino acid side chains at pH = 7.2. (Hint: Consider lessons from Coulomb's law, and the Henderson-Hasselbalch equation.)
Express your answers using two significant figures separated by a comma.
-0.99, 0.33