Problems http://edugen.wiley.com/edugen/courses/crs1900/rc/voet9301c06/dm9ld...

1. Draw a cis peptide bond and identify the groups that experience steric interference.

Answer:

2. Helices can be described by the notation nm, where n is the number of residues per helical turn and m is
the number of atoms, including H, in the ring that is closed by the hydrogen bond. (a) What is this
notation for the α helix? (b) Is the 310 helix steeper or shallower than the α helix?

Answer:

(a) 3.613;
(b) steeper.
3. Calculate the length in angstroms of a 100-residue segment of the α keratin coiled coil.

Answer:

(100 residues)(1 α-helical turn/3.6 residues) (5.1 Å/keratin turn) = 142 Å

4. Hydrophobic residues usually appear at the first and fourth positions in the seven-residue repeats of
polypeptides that form coiled coils. (a) Why do polar or charged residues usually appear in the remaining
five positions? (b) Why is the sequence Ile–Gln–Glu–Val–Glu–Arg–Asp more likely than the sequence
Trp–Gln–Glu–Tyr–Glu–Arg–Asp to appear in a coiled coil?

Answer:

(a) The first and fourth side chains of the two helices of a coiled coil form buried hydrophobic
interacting surfaces, but the remaining side chains are exposed to the solvent and therefore tend to
be polar or charged.
(b) Although the residues at positions 1 and 4 in both sequences are hydrophobic, Trp and Tyr are
much larger than Ile and Val and would therefore not fit as well in the area of contact between the
two polypeptides in a coiled coil.
5. Globular proteins are typically constructed from several layers of secondary structure, with a hydrophobic
core and a hydrophilic surface. Is this true for a fibrous protein such as α keratin?

Answer:

A fibrous protein such as α keratin does not have a discrete globular core. Most of the residues in its
coiled coil structure are exposed to the solvent. The exception is the strip of nonpolar side chains at the
interface of the two coils.

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6. The digestive tract of the larvae of clothes moths is a strongly reducing environment. Why is this
beneficial to the larvae?

Answer:

The reducing conditions promote cleavage of the disulfide bonds that cross-link α keratin molecules. This
helps the larvae digest the wool clothing that they eat.
7. Describe the primary, secondary, tertiary, and quaternary structures of collagen.

Answer:

Collagen's primary structure is its amino acid sequence, which is a repeating triplet of mostly
Gly–Pro–Hyp. Its secondary structure is the left-handed helical conformation characteristic of its
repeating sequence. Its tertiary structure is essentially the same as its secondary structure, since most of
the protein consists of one type of secondary structure. Collagen's quaternary structure is the arrangement
of its three chains in a right-handed triple helix.
8. Explain why gelatin, which is mostly collagen, is nutritionally inferior to other types of protein.

Answer:

Because collagen has such an unusual amino acid composition (almost two-thirds consists of Gly and Pro
or Pro derivatives), it contains relatively fewer of the other amino acids and is therefore not as good a
source of amino acids as proteins containing a greater variety of amino acids.
9. Is it possible for a native protein to be entirely irregular, that is, without α helices, β sheets, or other
repetitive secondary structure?

Answer:

Yes, although such irregularity should not be construed as random.

10. (a) Is Trp or Gln more likely to be on a protein's surface? (b) Is Ser or Val less likely to be in the protein's
interior? (c) Is Leu or Ile less likely to be found in the middle of an α helix? (d) Is Cys or Ser more likely
to be in a β sheet?

Answer:

(a) Gln; (b) Ser; (c) Ile; (d) Cys. See Table 6-1.
11. What types of rotational symmetry are possible for a protein with (a) four or (b) six identical subunits?

Answer:

(a) C4 and D2; (b) C6 and D3.

12. You are performing site-directed mutagenesis to test predictions about which residues are essential for a
protein's function. Which of each pair of amino acid substitutions listed below would you expect to
disrupt protein structure the most? Explain.

(a) Val replaced by Ala or Phe.

(b) Lys replaced by Asp or Arg.
(c) Gln replaced by Glu or Asn.
(d) Pro replaced by His or Gly.

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Answer:

(a) Phe. Ala and Phe are both hydrophobic, but Phe is much larger and might not fit as well in Val's
place.
(b) Asp. Replacing a positively charged Lys residue with an oppositely charged Asp residue would be
more disruptive.
(c) Glu. The amide-containing Asn would be a better substitute for Gln than the acidic Glu.
(d) His. Pro's constrained geometry is best approximated by Gly, which lacks a side chain, rather
than a residue with a bulkier side chain such as His.
13. Laboratory techniques for randomly linking together amino acids typically generate an insoluble
polypeptide, yet a naturally occurring polypeptide of the same length is usually soluble. Explain.

Answer:

A polypeptide synthesized in a living cell has a sequence that has been optimized by natural selection so
that it folds properly (with hydrophobic residues on the inside and polar residues on the outside). The
random sequence of the synthetic peptide cannot direct a coherent folding process, so hydrophobic side
chains on different molecules aggregate, causing the polypeptide to precipitate from solution.
14. Given enough time, can all denatured proteins spontaneously renature?

Answer:

No.
15. Describe the intra- and intermolecular bonds or interactions that are broken or retained when collagen is
heated to produce gelatin.

Answer:

Hydrophobic effects, van der Waals interactions, and hydrogen bonds are destroyed during denaturation.
Covalent cross-links are retained.
16. Under physiological conditions, polylysine assumes a random coil conformation. Under what conditions
might it form an α helix?

Answer:

At physiological pH, the positively charged Lys side chains repel each other. Increasing the pH above
the pK (>10.5) would neutralize the side chains and allow an α helix to form.
17. It is often stated that proteins are quite large compared to the molecules they bind. However, what
constitutes a large number depends on your point of view. Calculate the ratio of the volume of a
hemoglobin molecule (65 kD) to that of the four O2 molecules that it binds and the ratio of the volume of
a typical office (4 × 4 × 3 m) to that of the typical (70-kg) office worker that occupies it. Assume that
the molecular volumes of hemoglobin and O2 are in equal proportions to their molecular masses and that
the office worker has a density of 1.0 g/cm3. Compare these ratios. Is this the result you expected?

Answer:

The molecular mass of O2 is 32 D. Hence the ratio of the masses of hemoglobin and 4 O2, which is equal
to the ratio of their volumes, is 65,000/(4 × 32) = 508. The 70-kg office worker has a volume of 70 kg ×

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1 cm3/g × (1000 g/kg) × (1 m/100 cm)3 = 0.070 m3. Hence the ratio of the volumes of the office and the
office worker is (4 × 4 × 3)/0.070 = 686. These ratios are similar in magnitude, which you may not have
expected.
18. Which of the following polypeptides is most likely to form an α helix? Which is least likely to form a β
strand?

(a) CRAGNRKIVLETY
(b) SEDNFGAPKSILW
(c) QKASVEMAVRNSG

Answer:

Peptide c is most likely to form an α helix with its three charged residues (Lys, Glu, and Arg) aligned on
one face of the helix. Peptide a has adjacent basic residues (Arg and Lys), which would destabilize a
helix. Peptide b contains Gly and Pro, both of which are helix-breaking (Table 6-1). The presence of Gly
and Pro would also inhibit the formation of β strands, so peptide b is least likely to form a β strand.
19. The X-ray crystallographic analysis of a protein often fails to reveal the positions of the first few and/or
the last few residues of a polypeptide chain. Explain.

Answer:

In a protein crystal, the residues at the end of a polypeptide chain may experience fewer intramolecular
contacts and therefore tend to be less ordered (more mobile in the crystal). If their disorder prevents
them from generating a coherent diffraction pattern, it may be impossible to map their electron density.

Copyright © 2009 John Wiley & Sons, Inc. All rights reserved.

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