Essential Cell Biology 5th edition

148 CHAPTER 4 Protein Structure and Function
Figure 4−40 Enzymes can encourage
a reaction in several ways. (A) Holding
reacting substrates together in a precise
alignment. (B) Rearranging the distribution
of charge in a reaction intermediate.
(C) Altering bond angles in the substrate
to increase the rate of a particular reaction.
A single enzyme may use any of these
mechanisms in combination.
(A) enzyme binds to two
substrate molecules and
orients them precisely to
encourage a reaction to
occur between them
–
+
+
–
(B) binding of substrate
to enzyme rearranges
electrons in the substrate,
creating partial negative
and positive charges
that favor a reaction
(C) enzyme strains the
bound substrate
molecule, forcing it
toward a transition
state that favors a
reaction
for DNA synthesis during cell division. Because cancer cells have lost
important intracellular control systems, some of them are unusually sensitive
to treatments that interrupt chromosome replication, making them
susceptible to methotrexate.
Pharmaceutical companies often develop drugs by first using automated
methods to screen massive libraries of compounds to find chemicals that
are able to inhibit the activity of an enzyme of interest. They can then
chemically modify the most promising compounds to make them even
more effective, enhancing their binding affinity, specificity for the target
enzyme, and persistence in
ECB5
the human body. As we discuss in Chapter
20, the anticancer drug Gleevec ® 04.40
was designed to specifically inhibit an
enzyme whose aberrant behavior is required for the growth of a type of
cancer called chronic myeloid leukemia. The drug binds tightly in the
substrate-binding pocket of that enzyme, blocking its activity.
Tightly Bound Small Molecules Add Extra Functions to
Proteins
Although the precise order of their amino acids gives proteins their shape
and functional versatility, sometimes amino acids by themselves are not
enough for a protein to do its job. Just as we use tools to enhance and
extend the capabilities of our hands, so proteins often employ small,
nonprotein molecules to perform functions that would be difficult or
impossible using amino acids alone. Thus, the photoreceptor protein
rhodopsin, which is the light-sensitive protein made by the rod cells in
the retina of our eyes, detects light by means of a small molecule, retinal,
which is attached to the protein by a covalent bond to a lysine side chain
(Figure 4−41A). Retinal changes its shape when it absorbs a photon
of light, and this change is amplified by rhodopsin to trigger a cascade
of reactions that eventually leads to an electrical signal being carried to
the brain.
COOH
COOH
Figure 4−41 Retinal and heme are
required for the function of certain
proteins. (A) The structure of retinal, the
light-sensitive molecule covalently attached
to the rhodopsin protein in our eyes. (B) The
structure of a heme group, shown with the
carbon-containing heme ring colored red
and the iron atom at its center in orange.
A heme group is tightly, but noncovalently,
bound to each of the four polypeptide
chains in hemoglobin, the oxygen-carrying
protein whose structure was shown in
Figure 4−24.
H 3 C
(A)
CH 3
CH 3
CH 3
H 3 C
HC
O
H 3 C
H
H 2 C C
(B)
CH 2 CH 2
CH 2 CH 2
N N
Fe
N N
CH 3 HC
CH 2
CH 3
CH 3