SECTION 4.4
Tertiary Structure
57
FIGURE 4-8
Circular dichroism spectra for polypeptides with different conformations.
Note that for of-helix conformations, a characteristic “dip” is observed in
the region of
2 1 0
nm.
4.4 Tertiary Structure
Three-dimensional tertiary structure in proteins is main-
tained by ionic bonds, hydrogen bonds, -S -S - bridges,
van der Waals forces, and hydrophobic interactions.
The first protein whose tertiary structure was de-
termined
is
myoglobin,
an
oxygen-binding
protein
consisting of 153 amino acid residues; its structure was
deduced from x-ray studies by Kendrew, Perutz, et al. after
a 19-year analysis (Figure 4-9). Their studies provided
not only the first three-dimensional representation of
a globular protein but also insight into the important
bonding modes in tertiary structures. The major features
of myoglobin are described below.
1. Myoglobin is an extremely compact molecule with
very little empty space, accommodating only a small
number of water molecules within the overall
molecular dimensions of 4.5 x 3.5 x 2.5 nm. All of
the peptide bonds are planar with the carbonyl and
amide groups in trans configurations to each
other.
2. Eight right-handed «-helical segments involve
approximately 75% of the chain. Five nonhelical
regions separate the helical segments. There are two
nonhelical regions, one at the N terminus and another
at the C terminus.
3. Eight terminations of the a-helices occur in the
molecule, four at the four prolyl residues and the rest
at residues of isoleucine and serine.
4. Except for two histidyl residues, the interior of the
molecule contains almost all nonpolar amino acids.
The two histidyl residues interact in a specific manner
FIGURE 4-9
A high-resolution, three-dimensional structure of myoglobin.
with the iron of the heme group required for
myoglobin activity (Chapter 21). The exterior of the
molecule contains polar residues that are hydrated
and nonpolar amino acid residues. The amino acid
residues whose R-groups contain both polar and
nonpolar portions (e.g., threonine, tyrosine, and
tryptophan) are oriented so that the nonpolar group
faces inward and the polar group faces outward,
allowing only the polar portion to come in contact
with water.
5. Myoglobin has no S-S bridges that generally help
stabilize the conformation formed by amino acid
interactions.
Three-dimensional analyses of proteins other than myo-
globin reveal the incorporation of every type of secondary
structure into tertiary globular arrays. For example, triose
phosphate isomerase, a glycolytic enzyme (Chapter 13),
contains a core of eight
/3
-pleated sheets surrounded by
eight «-helices arranged in a symmetrical cylindrical bar-
rel structure known as
a
^-barrels (Figure 4-10). This
type of structure has also been noted among other gly-
colytic as well as nonglycolytic enzymes (e.g., catalase,
peroxidase). A few generalizations can be made. Larger
globular proteins tend to have a higher percentage of
hydrophobic
amino acids than do
smaller proteins.
