because of their dipole. A large proportion of the polar noncharged surface in the
interior did indeed comprise peptide bonds. (c) The terms polar and nonpolar do not
say much about the quantitative aspects of the solvation of these groups by water.
Note that the charged, i.e., very hydrophilic, groups were very predominantly at the
outside. Also, by far the greater part of the ‘‘true’’ hydrophobic residues (Leu, Ile,
Val, Phe, Trp) were observed to be in the core. Nevertheless, a large proportion of
the surface of the molecules in contact with the solvent consisted of, albeit not very
strongly, hydrophobic groups. This appears to be generally true for globular proteins
of fairly small size.
7.2 CONFORMATIONAL STABILITY AND
DENATURATION
In this section only globular proteins will be considered. Their tightly folded
native conformation (designated N) may change into a more or less
unfolded conformation (U). This change may be called denaturation, but
the conformation change may be reversible, and several authors reserve the
word denaturation for irreversible unfolding, or for the loss of a specific
activity.
The loss of the native conformation generally has several important
consequences:
- Loss of biological activity, notably enzyme activity, because
binding of molecules or groups is always involved, which depends in a
precise manner on the conformation of at least part of the protein molecule. - Decreasedsolubility, because more hydrophobic groups become
exposed to water. Also the surface activity may be altered. - Increasedreactivitywith other compounds or among groups on
the protein itself, because reactive side groups become exposed. In general,
most of the charged side groups are already exposed in the native state, such
as thee-amino groups of lysine, which are involved in the Maillard reaction.
Some other groups are mostly buried in the native state, notably the thiol
group of cysteine, which often becomes quite reactive when exposed. - Increased susceptibility toattack by proteolytic enzymes, because
peptide bonds inside a tightly-coiled protein molecule are not accessible to
these enzymes. - Increasedhydrodynamic sizeand its consequences; see Chapter 6.