Cellular Structure, Proteins, and Metabolism
67
of therapeutic drugs. For example, a drug (ligand) designed
to treat high blood pressure may act by binding to certain
proteins which, in turn, help restore pressure to normal. The
same drug, however, may also bind to a lesser degree to other
proteins, whose functions may be completely unrelated to
blood pressure.
Affi
nity
The strength of ligand-protein binding is a property of the
binding site known as
affi
nity.
The affi nity of a binding site
for a ligand determines how likely it is that a bound ligand
will leave the protein surface and return to its unbound state.
Binding sites that tightly bind a ligand are called high-affi nity
binding sites; those that weakly bind the ligand are low-affi nity
binding sites.
Affi nity and chemical specifi city are two distinct,
although closely related, properties of binding sites. Chemical
specifi city, as we have seen, depends only on the shape of the
binding site, whereas affi
nity depends on the strength of the
attraction between the protein and the ligand. Thus, differ-
ent proteins may be able to bind the same ligand—that is,
may have the same chemical specifi city—but may have differ-
ent affi nities for that ligand. For example, a ligand may have a
negatively charged ionized group that would bind strongly to
a site containing a positively charged amino acid side chain,
but would bind less strongly to a binding site having the same
shape but no positive charge (
Figure 3–29
). In addition, the
closer the surfaces of the ligand and binding site are to each
other, the stronger the attractions. Thus, the more closely the
ligand shape matches the binding site shape, the greater the
affi nity. In other words, shape can infl uence affi nity as well as
chemical specifi city.
Saturation
An equilibrium is rapidly reached between unbound ligands
in solution and their corresponding protein-binding sites.
Thus, at any instant, some of the free ligands become bound
to unoccupied binding sites, and some of the bound ligands
are released back into solution. A single binding site is either
occupied or unoccupied. The term
saturation
refers to the
fraction of total binding sites that are occupied at any given
time. When all the binding sites are occupied, the population
+
+
+
+
Ligands
Protein X
Protein Y
a
b
cc
a
b
c
Figure 3–27
Amino acids that interact with the ligand at a binding site need not
be at adjacent sites along the polypeptide chain, as indicated in this
model showing the three-dimensional folding of a protein. The
unfolded polypeptide chain appears at the bottom.
Figure 3–28
Protein X can bind all three ligands, which have similar chemical
structures. Protein Y, because of the shape of its binding site, can
bind only ligand c. Protein Y, therefore, has a greater chemical
specifi city than protein X.
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