4 Three-Dimensional Structure of Proteins
Conformational isomers of ethane (H
). Eclipsed and staggered
conformations for ethane are possible by virtue of the unrestricted rotation
about the carbon-carbon single bond. There is a potential energy difference
between the two forms, the staggered form being at the minimum and the
eclipsed form at the maximum.
particular conformation, changes such as
(protein unfolding) can lead to loss of biological activity.
Attractive and Repulsive Forces in Proteins
Both attractive and repulsive interactions occur among dif-
ferent regions of polypeptide chains and are responsible
for most secondary and tertiary structure.
Attractive Forces
Covalent bonds
involve the equal sharing of an electron
pair by two atoms. Examples of important covalent bonds
(amide) and
disulfide bonds
between amino
acids, and C-C, C-O, and C-N bonds within amino acids.
Coordinate covalent bonds
involve the unequal shar-
ing of an electron pair by two atoms, with both electrons
(originally) coming from the same atom. The electron pair
donor is the ligand, or Lewis base, whereas the acceptor
is the central atom (because it frequently can accept more
than one pair of electrons), or Lewis acid. These bonds
are important in all interactions between transition met-
als and organic ligands (e.g., Fe2+ in hemoglobin and the
Ionic interactions
arise from electrostatic attraction
between two groups of opposite charge. These bonds
are formed between positively charged (a-ammonium,
e-ammonium, guanidinium, and imidazolium) side chains
and negatively charged (ionized forms of a-carboxyl,
carboxyl, phosphate, and sulfate) groups.
Hydrogen bonds
involve the sharing of a hydrogen atom
between two electronegative atoms that have unbonded
electrons. These bonds, although weak compared to the
bonds discussed above, are important in water-water in-
teractions and their existence explains many of the unusual
properties of water and ice (Chapter 1). In proteins, groups
possessing a hydrogen atom that can be shared include
N-H (peptide nitrogen, imidazole, and indole), -SH (cys-
teine), -OH (serine, threonine, tyrosine, and hydroxypro-
line), -NH
and -NHjj" (arginine, lysine, and a-amino),
and -CONH
(carbamino, asparagine, and glutamine).
Groups capable of sharing a hydrogen atom include
-COO- (aspartate, glutamate, and a-carboxylate), -S -
(methionine), -S -S - (disulfide), and ^ C = 0 (in pep-
tide and ester linkages).
Van der Waals attractive forces
are due to a fixed dipole
in one molecule that induces rapidly oscillating dipoles in
another molecule through distortion of the electron cloud.
The positive end of a fixed dipole will pull an electron
cloud toward it; the negative end will push it away. The
strength of these interactions is strongly dependent on dis-
tance, varying as
/ r
is the interatomic separa-
tion. The Van der Waals forces are particularly important
in the nonpolar interior structure of proteins, where they
provide attractive forces between nonpolar side chains.
Hydrophobic interactions
cause nonpolar side chains
(aromatic rings and hydrocarbon groups) to cling together
in polar solvents, especially water. These interactions do
not produce true “bonds,” since there is no sharing of elec-
trons between the groups involved. The groups are pushed
together by their “expulsion” from the polar medium. Such
forces are also important in lipid-lipid interactions in mem-
Repulsive Forces
Electrostatic repulsion
occurs between charged groups
of the same charge and is the opposite of ionic (attractive)
forces. This kind of repulsion acts according to Coulomb’s
q\q2/r 2,
are the charges and
is the
interatomic separation.
Van der Waals repulsive forces
operate between atoms
at very short distances from each other and result from the
dipoles induced by the mutual repulsion of electron clouds.
Since there is no involvement of a fixed dipole (in contrast
to van der Waals attractive forces), the dependence on
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