Amino acids and protein chemistry sample question 2

competing with the histidine side chains for coordination sites on the immobilized Ni²⁺.

Amino acids and protein chemistry sample question 3

contains nearby negative charges that stabilize the protonated imidazolium form.

MCAT · Chemical and Physical Foundations · Biochemistry

Amino acids and protein chemistry

Amino acids and protein chemistry is part of Biochemistry in the MCAT Chemical and Physical Foundations section. The questions below are written in the style of the real test, each with the answer and a worked explanation.

Question types you will see here include amino acid and peptide charge versus pH, isoelectric point and migration, side-chain classification and placement and peptide bond and sequence notation.

Common traps: giving the side chain the wrong charge; forgetting the terminal groups of a peptide; taking protonated as charged for every group.

Sample questions

Question 1
Which amino acid is most likely to be found on the lipid-facing surface of a transmembrane α-helix?
- A.
  Leucine
- B.
  Aspartate
- C.
  Lysine
- D.
  Serine
Answer: A. Leucine
The lipid-facing surface of a membrane-spanning helix contacts hydrocarbon chains, so nonpolar residues such as leucine, isoleucine, valine, and phenylalanine predominate there. Aspartate and lysine are charged and would be enormously costly to bury in the bilayer, and serine's hydroxyl prefers water or hydrogen-bonding partners.
Question 2
A recombinant protein carrying a hexahistidine tag is purified on a nickel-affinity column and eluted with a buffer containing imidazole. The imidazole works by:
- A.
  denaturing the protein so that it no longer fits the column's pores.
- B.
  competing with the histidine side chains for coordination sites on the immobilized Ni²⁺.
- C.
  raising the pH so that the histidines become negatively charged.
- D.
  cleaving the tag from the rest of the protein.
Answer: B. competing with the histidine side chains for coordination sites on the immobilized Ni²⁺.
The tag binds because the imidazole rings of histidine coordinate the immobilized Ni²⁺; free imidazole at high concentration occupies those sites and displaces the protein, which then washes off intact. The protein is neither denatured nor cleaved, and histidine's imidazole never becomes negatively charged in aqueous buffer.
Question 3
A histidine in an enzyme's active site has an apparent side-chain pKa of 7.5, compared with about 6.0 for free histidine. Its microenvironment most likely:
- A.
  contains nearby negative charges that stabilize the protonated imidazolium form.
- B.
  contains nearby positive charges that stabilize the protonated form.
- C.
  is nonpolar, which favors the charged form of the side chain.
- D.
  is fully exposed to water, which raises every pKa.
Answer: A. contains nearby negative charges that stabilize the protonated imidazolium form.
A higher pKa means the protonated (cationic) form persists to a higher pH, so something stabilizes the positive charge: nearby carboxylates (Asp or Glu) do this electrostatically. Nearby positive charges would repel the proton and lower the pKa, a nonpolar pocket disfavors the charged form and also lowers it, and full exposure to water simply returns the pKa toward the free-histidine value.

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