Lecture 8 ~ Protein Structure Practice Questions

A 24-year-old graduate student is performing an experiment in which an enzyme is used to interconvert two stereoisomeric forms of the same amino acid in solution. To confirm which stereoisomer is present, she draws a Fischer projection with the carboxyl group at the top and observes that the amino group lies to the right. She then plans to incorporate this amino acid into a ribosomally synthesized peptide. Which of the following conclusions is most accurate?

• A. The amino acid is the D-isomer, and it is not the preferred form used to build proteins
  

• B. The amino acid is the L-isomer, and it rotates polarized light clockwise
  

• C. The amino acid is the D-isomer, and it rotates polarized light counterclockwise
  

• D. The amino acid is achiral because all α-amino acids lack four distinct substituents
  

• E. The solution must be racemic because enzymes that interconvert stereoisomers always produce 50/50 mixtures

Answer explanation

Your answer: A — ✅ Correct

Why this is right:

• In a Fischer projection with the carboxyl group at the top:

  • NH₂ on the right = D-amino acid

• Ribosomally synthesized proteins use L-amino acids, so a D-amino acid is not the preferred biological form.

Why the others are wrong (high-yield):

• B/C: D/L designation has no relationship to optical rotation direction.

• D: Almost all α-amino acids are chiral (glycine is the exception).

E: Enzymatic interconversion does not imply a racemic mixture.

A researcher designs a synthetic peptide that must form a stable, rod-like right-handed α-helix for a drug-delivery scaffold. After testing several variants, one version repeatedly fails to form a stable helix under physiologic conditions. Compared with the successful scaffold, the failed peptide has been enriched in Pro, Gly, Thr, Val, Ile, Ser, Asp, and Asn. Which amino acid change would be most likely to rescue α-helix formation based on residue preferences described in the lecture?

• A. Replace several residues with Tyr, Trp, and Phe
  

• B. Replace several residues with Met, Ala, Arg, Lys, and Leu
  

• C. Replace several residues with Thr, Val, and Ile
  

• D. Replace residue 2 of multiple turns with Proline
  

• E. Replace multiple residues with Aspartate and Asparagine to increase backbone hydrogen bonding

Answer explanation

Your answer: B — ✅ Correct

Why this is right:

• Amino acids that stabilize α-helices include:

  • Met, Ala, Leu, Arg, Lys

• The failed peptide was enriched in helix breakers:

  • Pro (rigid ring, no amide H)

  • Gly (too flexible)

  • β-branched residues (Val, Ile)

  • Polar residues that disrupt packing (Ser, Asp, Asn)

NBME pearl:

α-helix stability = side chains that allow tight packing + uninterrupted H-bonding

3. A 19-year-old patient has recurrent kidney stones. Urinalysis has a characteristic odor, and testing suggests abnormal renal handling of several basic amino acids in addition to the molecule responsible for the odor. The clinician explains that the underlying problem involves a covalent linkage formed between two identical amino acid side chains to create a new residue. Which type of bond is being referenced?

• A. Hydrogen bonds along the peptide backbone
  

• B. Ionic interactions between oppositely charged R groups
  

• C. Hydrophobic clustering of nonpolar R groups in the protein interior
  

• D. Disulfide bond formation between two cysteine residues
  

• E. Peptide bond formation between an α-amino group and an α-carboxyl group

Answer explanation

Correct answer: D was actually right conceptually, but your mapping is off — let’s clarify why this was a trap.

This vignette describes cystinuria, which involves:

• Cysteine forming a disulfide bond → cystine

• Poor solubility → kidney stones

The bond referenced is:
👉 Disulfide bond between two cysteine residues

So D is correct, but this question tested clinical correlation + covalent chemistry, not just “protein folding.”

You got this right, but it’s worth noting why it’s commonly misread.

A 9-year-old child has episodic pain crises and jaundice. During hypoxic stress testing, their red blood cells become rigid and distorted, and capillary flow is impaired. Genetic testing identifies a missense change in the β-globin gene that replaces a hydrophilic, polar, charged amino acid with a hydrophobic, nonpolar, neutral amino acid at position 6. Under low oxygen tension, the abnormal hemoglobin forms rod-like precipitates. Which interaction most directly promotes the abnormal hemoglobin molecules sticking together in this setting?

• A. Hydrogen bonding between peptide backbone carbonyl and amide groups
  

• B. Ionic “salt bridge” formation between charged R groups
  

• C. Hydrophobic interactions among nonpolar side chains
  

• D. Covalent peptide bonds forming between separate hemoglobin molecules
  

• E. Enzymatic ubiquitination targeting hemoglobin for proteasomal degradation

A buffer is prepared by mixing 2.5 mM formic acid (HA) with 25 mM sodium formate (A⁻). The pKₐ of formic acid is 3.75. Which of the following is the best estimate of the pH of this solution?

• A. 2.75
  

• B. 3.75
  

• C. 4.75
  

• D. 5.75
  

• E. 6.75