Biochemistry Lecture 6

Q: What causes flexibility in the polypeptide backbone?

A: Rotation about single bonds.

Q: What are the two main types of secondary structure?

A: α-helix and β-sheet.

What determines which secondary structure forms?

The local amino acid sequences.

Q: What are the three classes of amino acids based on structure preference?

A: β-sheet formers (bulky side chains), α-helix formers, and structure breakers.

What is the secondary structure?

Regular repetitive patterns in short regions of the polypeptide chain.

Q: What happens to proteins in the denatured state?

A: They lose orderly arrangement and become non-functional.

Q: What is the ordered functional form of a protein called?

The native state.

Q: What technique revealed protein repetitive structures?

X-ray diffraction

Q: Which proteins were studied to discover α and β structures?

A: Keratins→ a fibrous protein (α-keratin and β-keratin/fibroin).

Q: Who discovered the structural basis of secondary structures?

A: Linus Pauling.

Q: Why is the peptide bond rigid?

A: Resonance gives it partial double-bond character.

Q: What is the length of the peptide bond?

About 1.32 Å.

Q: Can the peptide bond rotate freely?

A: No, it can only form cis or trans isomers (usually trans).

Q: Where can rotation occur in the polypeptide chain?

A: Around the α-carbon atoms.

Q: What are Pauling’s two stable backbone patterns?

A: Helical (α-helix) and extended (β-sheet).

Q: What causes instability in other arrangements?

A: Steric clashes between atoms.

Q: How many amino acids per turn are in an α-helix?

A: 3.6 amino acids per turn.

Q: What bonds stabilize the α-helix?

A: Hydrogen bonds between C=O of residue i and N-H of residue i+4.

Q: What is the rise per amino acid in an α-helix?

A: 1.5 Å

What is the distance per turn in an a-helix

5.4 A

Which handedness is found in natural alpha helices?

Right handed.

What type of structure forms from parallel or antiparallel extended strands. 

B-sheet

Q: Which β-sheet arrangement is more stable?

Anti parallel.

Q: What pattern do side chains show in β-sheets?

A: Alternate up and down (zig-zag).

Q: Why do bulky side chains prefer β-sheets?

A: β-sheets leave more space for large side chains.

Q: Which amino acids prefer β-sheets?

A: Tyr, Trp, Phe, Ile, Val, Thr, Cys.

Q: What is the main criterion for α-helix preference?

A: The main criterion for α-helix preference is having side chains that don’t interfere with the helix’s internal hydrogen bonds

Q: Which amino acids prefer α-helices?

A: Ala, Leu, Met, Phe, Glu, Gln, His, Lys, Arg.

Q: Which amino acids break secondary structure?

A: Gly, Pro, Asn, Asp, Ser.

Q: Why does Gly disrupt structure?

A: Its side chain (H) is too small to protect H-bonds.

Q: Why does Pro disrupt structure?

A: Its side chain bonds to backbone N, blocking H-bond formation.

Q: How do Asn, Asp, and Ser disrupt structure?

A: Their side chains form competing H-bonds with the backbone.

**Note: Glu and Gln, however, have longer side chains, so their polar groups are farther away from the backbone. Because they can’t easily reach back to the backbone, they’re less likely to interfere — and in fact, they sometimes even stabilize helices through external interactions.

Q: What are regions linking secondary structures called?

Loops or turns.

Q: What defines α-helix formation likelihood?

A: ≥60% helix formers, ≤20% breakers in runs of ≥6 amino acids.

Q: What defines β-sheet formation likelihood?

A: ≥60% β-sheet formers, ≤20% breakers in runs of ≥5 amino acids.

Q: What typically initiates a turn or loop?

A: Two or more breakers in a run of four amino acids.

Q: How do amino acids select secondary structure?

A: By consensus within a local sequence, not individually.