I don\'t get the explanation to this question. Why would histidine lose its posi

Question

I don't get the explanation to this question. Why would histidine lose its positive charge when the pKa is lowered? Isn't the common pka value for histidine at 6? So wouldn't it lose a proton at pka = 6 or greater? Please explain!

7. For the protein you are studying you have determined the protein structure and there is a lysine side chain near a histidine side chain. What would you expect to be true for the pKa values of these amino acid side chains given their close proximity in this protein would the pK, values be higher, lower or relatively unchanged and explain why? (6 points) Since these are both basic amino acids which are both positively charged at pH values below 6 (the pKa for histidine), the expectation is that the pKa for at least the histidine will be lowered (below 6). The two positive charges in close proximity would be unfavorable since like charges repel and this is the reason why the pK would be lowered such that histidine loses its positive charge and is now a hydrogen bonding partner and not repelled by the lysine side chain. For lysine you would expect either to see the pKa lowered in order to maximize the ability to hydrogen bond with the histidine side chain or unaltered, it would most likely not be higher. Vou haie mivture of fte nrtinae deecribed in the table helou ueo thie to aneer

Explanation / Answer

pK of amino acids is not a constant. They contain different pk values depending upon their surroundings. Amino acids in protein native structures exhibit diverse pK values in different microenvironments.

In the microenvironment of native protein structure, the dissociation of amino acids is affected by their neighbouring groups.

For example, if an acidic amino acid is placed near another acidic amino acid, the propensity to lose proton will be increased.

Similarly, if a positive amino acid is placed near another positive amino acid, the propensity to lose a proton will be reduced.

In the given case, His and Lys are close together in a protein. pK is the pH above which a functional group loses a proton. Lys reduces the pK of His so that it can lose proton even at low pH.

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