Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

144 Chapter 3: Proteins
Figure 3–47 Enzymatic acceleration of chemical reactions by decreasing
the activation energy. There is a single transition state in this example.
However, often both the uncatalyzed reaction (A) and the enzyme-catalyzed
reaction (B) go through a series of transition states. In that case, it is the
transition state with the highest energy (S T and ES T ) that determines the
activation energy and limits the rate of the reaction. (S = substrate;
P = product of the reaction; ES = enzyme–substrate complex; EP = enzyme –
product complex.)
Because this tight binding greatly lowers the energy of the transition state, the
enzyme greatly accelerates a particular reaction by lowering the activation energy
that is required (Figure 3–47).
Enzymes Can Use Simultaneous Acid and Base Catalysis
Figure 3–48 compares the spontaneous reaction rates and the corresponding
enzyme-catalyzed rates for five enzymes. Rate accelerations range from 10 9 to
10 23 . Enzymes not only bind tightly to a transition state, they also contain precisely
positioned atoms that alter the electron distributions in the atoms that participate
directly in the making and breaking of covalent bonds. Peptide bonds, for example,
can be hydrolyzed in the absence of an enzyme by exposing a polypeptide to
either a strong acid or a strong base. Enzymes are unique, however, in being able
to use acid and base catalysis simultaneously, because the rigid framework of the
protein constrains the acidic and basic residues and prevents them from combining
with each other, as they would do in solution (Figure 3–49).
The fit between an enzyme and its substrate needs to be precise. A small
change introduced by genetic engineering in the active site of an enzyme can
therefore have a profound effect. Replacing a glutamic acid with an aspartic acid
in one enzyme, for example, shifts the position of the catalytic carboxylate ion by
only 1 Å (about the radius of a hydrogen atom); yet this is enough to decrease the
activity of the enzyme a thousandfold.
energy
S
activation energy
for uncatalyzed reaction
ES
S T
ES T
A
EP
progress
of reaction
activation energy
for catalyzed reaction
B
MBoC6 m3.46/3.43
P
Lysozyme Illustrates How an Enzyme Works
To demonstrate how enzymes catalyze chemical reactions, we examine an enzyme
that acts as a natural antibiotic in egg white, saliva, tears, and other secretions.
Lysozyme catalyzes the cutting of polysaccharide chains in the cell walls of bacteria.
The bacterial cell is under pressure from osmotic forces, and cutting even a
small number of these chains causes the cell wall to rupture and the cell to burst.
A relatively small and stable protein that can be easily isolated in large quantities,
lysozyme was the first enzyme to have its structure worked out in atomic detail by
x-ray crystallography (in the mid-1960s).
The reaction that lysozyme catalyzes is a hydrolysis: it adds a molecule of water
to a single bond between two adjacent sugar groups in the polysaccharide chain,
thereby causing the bond to break (see Figure 2–9). The reaction is energetically
favorable because the free energy of the severed polysaccharide chain is lower
half-time for reaction
10 6 years 1 year 1 min
1
msec
1
µsec
OMP decarboxylase
staphylococcal nuclease
adenosine deaminase
triosephosphate
isomerase
carbonic
anhydrase
UNCATALYZED
CATALYZED
Figure 3–48 The rate accelerations
caused by five different enzymes.
(Adapted from A. Radzicka and
R. Wolfenden, Science 267:90–93, 1995.)