The side chain of histidine has a typical pKa value in the range of 6.5-7.4. However, when analyzing the pKa values in a particular protein, scientists determined that one particular His residue has an unusually low pKa value of 4.8. Which of the following statements correctly explain this anomaly?
1) The microenvironment around a residue can impact its pKa value.
2) A positively charged amino acid must be in close proximity to this residue.
3) A negatively charged amino acid must be in close proximity to this residue.
Statements 1 and 2 are correct.
Statements 1 and 4 are correct.
Statements 1, 2, and 4 are correct.
Statements 2, 3, and 4 are correct.
4) This residue must be located on the surface of the protein.