a 10 pts Amino acid side chain pKa values shift relative tot

a) [10 pts Amino acid side chain pKa values shift relative tothe pKa in water when the side chains are placed in different protein environments. Predict the direction of the side chain pKa shift (up or down in the following environments: Protein environment Hydrophobic Positively-charged Negatively-charged Asp Lys b) 10 ptsl The pKa of His72 in bovine protein tyrosine phosphatase is shifted relative to a His side chain in water. Use the structure of this protein in the pdb file 1PNT to examine the environment surrounding His72 (functional groups within 5 A of the His side chain). Predict the direction of the pKa shift and provide a brief explanation.

Solution

1. Asp is an amino acid with negatively charged side chain (pKr is 3.86)
Lys is an amino acid with a positively charged R group (pKr is 10.54)

For positively charged environment
* Lys - pKa - 8.95 (decrease)
* Asp- pKa - 9.82 (decrease)

For positively charged environment
* Lys - pKa - 8.95 (decrease)
* Asp- pKa - 9.82 (decrease)

For negatively charged environment
* Lys - pKa - 2.18 (decrease)
* Asp- pKa - 2.09 (decrease)

For hydrophobic environments, due to non polar envirnments, the pKa for Lys will decrease. Asp pKa will increase in case of a hydrophobic environment as it is an acidic amino acid.