Question

1. Based on pKa values, which amino acid side chains are easiest to protonate and deprotonate at cellular pH (7.4)? (Choose all that apply)

Aspartic Acid

Histidine

Lysine

Serine

Arginine

Glutamic Acid

Cysteine

Tyrosine

2. At pH 7.4, which of the amino acid sidechains or R-groups below will be mostly deprotonated? (Chose all that apply)

Glutamatic Acid

Aspartic Acid

Arginine  

Tyrosine

Serine  

Lysine  

Histidine

Cysteine

3. Acetyltransferase enzymes modify a lysine side chain with an acetyl group. Titration of the pKa of the lysine substrate reveals the pKa value to be 8.1. What is the likely environment surrounding the lysine sidechain before it is acetylated? (Choose all that apply)

Cannot hypothesize based on the given information and prior knowledge  

Water accessible active site in the enzyme

Water inaccessible highly polar active site

Largely non-polar and water inaccessible active site

Solvent exposed and near the enzyme surface

Answer 1

Aspartic acids, Glutamic acid have very low pKa value so they lose a proton, and becomes negatively charged at pH 7.4. So they are prone to deprotonation.

Aminoacids like Arginine, Lysine, Histidine have a larger Pka that they tend to gain a proton and becomes positively charged. So they are protonated at pH 7.4.

Serine, Tyrosine, and cysteine will also get deprotonated but at very slow rate as they have very less difference in the PKa value.

Ans. The pI value of side chains of aspartic acid and glutamic acid is lesser than the Pka value at pH 7.4, so they are more prone to deprotonation.

Ans. Water inaccessible highly polar active site is the condition when there will be a negative charge on the lysine that can facilitate the addition of acetyl group to the lysine side chain.