Question

Indicate which of the amino acid residues in the following peptide sequence contains a group that has a negative charge for its most likely charge state at pH 4. Met-Tyr-Ile-Trp-Gln-Val-Cys-Pro-Lys

Answer 1

Side chain of Met or methionine residue is -CH₂CH₂-S-CH₃; it contains a thioether group and the side chain cannot carry negative charge at pH 4.

Side chain of Tyr or tyrosine residue is -CH₂-C₆H₄OH; it contains a phenolic group which cannot carry negative charge at pH 4.

Side chain of Ile or isoleucine residue is sec-butyl group which cannot carry negative charge at pH 4.

Side chain of Trp or tryptophan residue contains an indole group which does not carry negative charge at pH 4.

Side chain of Gln or glutamine residue contains an amide group which does not carry negative charge at pH 4.

Side chain of Val or valine residue is isopropyl group which cannot carry negative charge at pH 4.

Side chain of Cys or cysteine residue is CH₂SH group which will not carry negative charge at pH 4

Pro or Proline residue contains a alkyl side chain whose other end is bonded to the nitrogen atom. It cannot carry negative charge at pH 4.

Side chain of Lysine residue is -(CH₂)₄NH₂ and it will not carry negative charge at pH 4 as amino group will be protonated.

Thus, none of the side chains of different amino acid residues in given peptide sequence can carry negative charge at pH 4.

The N-terminus of given peptide sequence is methionine (Met) and C-terminus is Lysine. pK_a for -COOH group of lysine in the free amino acid is quite low and equal to 2.18. Low value of pK_a implies high value of K_a (acid dissociation constant) and tendency of the carboxylic acid group to be in ionized form, that is, in carboxylate form(-COO^-). The pK_a values for ammonium group (-NH₃⁺) of methionine and for ammonium group (-NH₃⁺) in side chain of lysine, are quite high (9.21 and 10.53 respectively) which implies that the respective acid dissociation constants are low or in other words the -NH₃⁺ groups have little tendency to give up H⁺ ions at pH lower than their pK_a values.

Hence, at pH 4 which is above 2.18, lysine residue will have carboxylate group(-COO^-) and the amino group of methionine as well as amino group in side chain of lysine will be protonated.

Answer: Lys or Lysine is the amino acid residue in given peptide sequence, which contains group that has negative charge at pH 4. The group is carboxylate group (-COO^-) of lysine.