Chem 365
Problem Set 5 Answer Key
1. Covalent cross-linking contributes significantly to the strength and rigidity of collagen fibers. In one
type of cross-link, allysine residues condense with lysine residues to form a Schiff base. When an
allysine residue reacts with homocysteine, it is unable to participate in the normal cross-linking of
collagen molecules. High levels of homocysteine in blood probably leads to defective collagen structure
and skeletal deformities.
See bulletin board for reaction
2. a) Nucleophilic attack by an imidazole nitrogen of His57 on the –CH2- carbon of the chloromethyl group of
TPCK covalently inactivates chymotrypsin.
See bulletin board for reaction.
b) TPCK is specific for chymotrypsin because the phenyl ring of the Phe residue interacts effectively
with the binding pocket of the chymotrypsin active site. This positions the chloromethyl group to
react with His57. This reaction and binding occurs in the same way as peptide binding and
hydrolysis.
c) Replacement of the Phe residue of TPCK with arginine or lysine produces reagents that are specific
for trypsin.
3. 6, 2, 2 (both antigens are exactly the same), no, 1, 1
4. See page 163 in book.
The myoglobin polypeptide chain is folded to form a cradle that nestles the heme prosthetic group. The
Fe(II) in the heme is coordinated to 4 nitrogen atoms of the four pyrroles. The fifth ligand is donated by the
imidazole side chain of amino acid residue His F8 in the myoglobin molecule holding the heme group in
place. The polypeptide of myoglobin can be viewed as serving three critical functions: it cradles the heme
group, it protects the heme iron atom from irreversible oxidation, and it provides a pocket into which the O2
can fit.
5. Myoglobin is abundant in skeletal and cardiac muscle, because the major physiological role of myoglobin is
to facilitate oxygen transport in muscle. Oxygenation of the heme group alters the electronic state of the
Fe(II)-heme complex causing it to appear red, thus giving muscle its characteristic red color.
6. The first 108 amino acids of the light chain are variable. Likewise, the first 108 amino acids of the heavy
chain are variable as well. These variable regions form the antigen-binding site of the molecule. It is the
amino acid sequence in these binding sites that will determine what antigen can bind to the site. The
interactions between the antigen and antibody are noncovalent and include van der Waals, H-bonding, and
hydrophobic interactions. Ionic salt bridges participate in the association to a much lesser extent. These
variable amino acid sequence regions are crucial to the body’s ability to produce antibodies capable of
binding all types of antigens.