Essential Cell Biology 5th edition

146 CHAPTER 4 Protein Structure and Function
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(A) S + E ES EP E + P (B)
Figure 4−38 Lysozyme cleaves a polysaccharide chain. (A) Schematic view of the enzyme lysozyme (E), which
catalyzes the cutting of a polysaccharide substrate molecule (S). The enzyme first binds to the polysaccharide to
form an enzyme–substrate complex (ES), then it catalyzes the cleavage of a specific covalent bond in the backbone
of the polysaccharide. The resulting enzyme–product complex (EP) rapidly dissociates, releasing the products (P)
and leaving the enzyme free to act on another substrate molecule. (B) A space-filling model of lysozyme bound to
a short length of polysaccharide chain prior to cleavage.
ECB5 04.38
without being hydrolyzed to any detectable degree. This is because there
is an energy barrier to such reactions, called the activation energy (discussed
in Chapter 3, pp. 89–90). For a colliding water molecule to break a
bond linking two sugars, the polysaccharide molecule has to be distorted
into a particular shape—the transition state—in which the atoms around
the bond have an altered geometry and electron distribution. To distort
the polysaccharide in this way requires a large input of energy—which is
where the enzyme comes in.
Like all enzymes, lysozyme has a binding site on its surface, termed an
active site, which is where catalysis takes place. Because its substrate is
a polymer, lysozyme’s active site is a long groove that cradles six of the
linked sugars in the polysaccharide chain at the same time. Once this
enzyme–substrate complex forms, the enzyme cuts the polysaccharide
by catalyzing the addition of a water molecule to one of its sugar–sugar
bonds, and the severed chains are then quickly released, freeing the
enzyme for further cycles of cleavage (Figure 4−38).
Like any protein binding to its ligand, lysosome recognizes its substrate
through the formation of multiple noncovalent bonds (see Figure 4−32).
However, lysozyme holds its polysaccharide substrate in such a way that
one of the two sugars involved in the bond to be broken is distorted from
its normal, most stable conformation. Conditions are thereby created
in the microenvironment of the lysozyme active site that greatly reduce
the activation energy necessary for the hydrolysis to take place (Figure
4−39). Because the activation energy is so low, the overall chemical reaction—from
the initial binding of the polysaccharide to the final release of
the severed chains—occurs many millions of times faster in the presence
of lysozyme than it would in its absence. In the absence of lysozyme, the
energy of random molecular collisions almost never exceeds the activation
energy required for the reaction to occur; the hydrolysis of such
polysaccharides thus occurs extremely slowly, if at all.
Other enzymes use similar mechanisms to lower the activation energies
and speed up the reactions they catalyze. In reactions involving two or
more substrates, the active site acts like a template or mold that brings
the reactants together in the proper orientation for the reaction to occur
(Figure 4−40A). As we saw for lysozyme, the active site can also contain
precisely positioned chemical groups that speed up the reaction by
altering the distribution of electrons in the substrates (Figure 4−40B).