BMED11-205 Medical Chemistry 1 2010

Tutorial Guide - Week 5 - 3D Protein Structure

Question 1
The three-dimensional conformation of a protein may be strongly influenced by amino acid residues
that are very far apart in sequence. This relationship is in contrast to secondary structure, where the
amino acid residues are:

(a) always side by side.

(b) generally near each other in sequence.
(c) invariably restricted to about 7 of the 20 standard amino acids.
(d) often on different polypeptide strands.
(e) usually near the polypeptide chain’s amino terminus or carboxyl terminus.

Question 2
Draw a dipeptide of 2 amino acids in trans linkage (side chains can be shown by –R), and
indicate the 6 atoms that make up the planar structure of the peptide bond

Question 3
Which of the following statements is false?

(a) Collagen is a protein in which the polypeptides are mainly in the -helix conformation.
(b) Disulfide linkages are important for keratin structure.
(c) Gly residues are particularly abundant in collagen.
(d) Silk fibroin is a protein in which the polypeptide is almost entirely in the  conformation.
(e) -keratin is a protein in which the polypeptides are mainly in the -helix conformation.

NB. Collagen is composed of left handed helices different to the alpha-helix

Question 4
What are the 4 levels of protein structure and give an example of each.
ANS.
Primary – amino acid sequence (LGYVHPFFA FDDEWQILQ etc)
Secondary – alpha helix or beta conformation
Tertiary – globular protein eg. Myoglobin
Quarternary – multimeric protein such as Haemoglobin
 BMED11-205 Medical Chemistry 1 2010

Question 5
In the a-helix, the hydrogen bonds are
(a) Roughly parallel to the axis of the helix
(b) Are roughly perpendicular to the axis of the helix
(c) Occur mainly between electronegative atoms of the R groups
(d) Occur only between some of the amino acids of the helix
(e) Occur only near the amino and carboxyl termini of the helix

Question 6
Explain what is meant by motifs in protein structure.
Answer:

Motifs are particularly stable arrangements of elements of secondary structure (e.g.,  helix and 
conformation), including the connections between them, which are found in a variety of proteins.
Common folding patterns

Question 7
How can changes in pH alter the conformation of a protein?
Answer:

Changes in pH can influence the extent to which certain amino acid side chains (or the amino and
carboxyl termini) are protonated. The result is a change in net charge on the protein, which can lead
to electrostatic attractions or repulsions between different regions of the protein. The final effect is
a change in the protein’s three-dimensional shape or even complete denaturation.

Question 8
Our growing understanding of how proteins fold allows us to make predictions of protein structure
based on primary sequence data. Consider the following sequences:-

1 2 3 4 5 6 7 8 9 10
Lle Ala Hig Thr Tyr Gly Pro Phe Glu Ala
11 12 13 14 15 16 17 18 19 20
Ala Met Cys Lys Trp Glu Ala Gln Pro Asp
21 22 23 24 25 26 27 28
Gly Met Glu Cys Ala Phe His Arg

(a) Where might bends or -turns occur?

Answer:

Bends of turns are most likely to occur at residue 7 ad 19 because PRO residues are often (but not
 BMED11-205 Medical Chemistry 1 2010

always) found at bends in globular proteins. A bend may also occur at the THR residue (residue 4)
and, assuming that this is a portion of a larger polypeptide at the ILE residue (res 1)

(b) Where might intra-chain disulphide cross-linkages be formed?

Answer:

Intra chain disulphide cross-linkages can form only between residues 13 & 24 (ie CYS residues)

(c) Assuming that this sequence is part of a larger globular protein, indicate the probable
location (the external surface or interior of the protein) of the amino acid residues below.
Explain your reasoning. (HINT: See the hydropathy index in Table 3-1 of Lehninger )

Answer:

ASP ILE THR ALA GLN LYS.

external Internal Internal Internal External external

AAs with strongly polar or ionic are located on the external surface.
REsdues with non-polar side chains (eg ALA and ILE) are located on the interior where they escape
polar environment. THR is of intermediate polarity and could be found at both places.

Question 9