Question

The pKa of an aspartic acid side chain buried in the hydrophobic core of a protein is found to be unusually high. Explain in your own words why this might be the case.

Answer 1

Answer-

According to the given question-

• We know that the pKa values of ionizable groups present at the interior of the hydrophobic core of a protein are different than normal pKa of the ionizable groups present in the water.
• pKa of the aspartic acid side chain is creating the imbalance between the polar interactions that are favorable while the dehydration, as well as Coulomb interactions with their carboxylic groups found at the surface, is unfavorable and their ionization is generally coupled with the structural reorganization.
• Due to these, there is a complex interaction that occurs between the structural reorganization, Coulomb interactions as well as local polarity responsible for determining the pKa values of proteins internal groups in proteins.
• So the ionization of internal groups depends upon the conformational reorganization, that determines the pKa value.
• The small portion of ionizable residues inside proteins are buried in the interior part of the protein , due to the water, required for molecular recognition, transport of H⁺/e^-, as well as catalysis, thus are very specific for biological purposes.
• The change in pKa of the group present in the interior are governed by differences created due to polarizability and polarity, and present of charge in these two environments, as well as the Coulomb interactions and the charges, present on the other ionizable groups of a protein.
• The Structural reorganization inside the protein is related to the internal group ionization and due to which the valve of pKa is changed.
• The polarizability and polarity inside the interior of a protein are generally has a lower than that found in water, due to which the valve of ΔG_self is unfavorable for ionizable groups that are buried inside the interior of the protein.
• Due to which the pKa values of ionizable groups present interior, shift in the neutral state which means that the value of pKa for acidic groups is increasing and for basic groups decreases.