BioPHYSICAL chemistry

Enzyme mechanisms

Although the specific mechanism by which

enzymes stabilize the transitional state is

unique for each protein, the general mech-

anism can be understood in terms of an

enhancement of the stability of the transition

state. In a simple picture (Figure 7.12), consider an enzyme designed to

break a bond in a molecule. Normally the molecule is stable but binding

of the molecule to the enzyme bends the molecule such that a specific

bond is positioned for catalytic cleavage. The enzyme provides multiple

weak interactions between the enzyme and substrate that are specific-

ally positioned such that binding is optimized for the intermediate state.

These interactions not only facilitate the reaction but also are designed

for specificity, with binding constants several orders of magnitude larger

for the substrate than for analogous molecules.

Research direction: dynamics in enzyme mechanism

Proteins are not static molecules, they undergo dynamical rearrangements

constantly (Frauenfelder et al. 1991). Proteins can undergo large-scale

conformational changes on a millisecond timescale. For example, oxygen

transport by hemoglobin is regulated by cooperative conformational

changes. Even if proteins do not undergo large structural changes, they

do undergo constant fluctuations with motions occurring on timescales as

short as picoseconds (see Chapter 8). To some degree, such motions are

inherent due to the nature of molecules in solution. However, enzymes may

have evolved to make use of such motions in order to more efficiently

perform catalysis.

150 PARTI THERMODYNAMICS AND KINETICS

Table 7.2

Representative values of Keqand ΔG° using eqn 3.20.

Keq ΔΔG° (kJ mol−−^1 )

10 −^5 28.5

10 −^3 17.1

10 −^1 5.7

10

101 −5.7

103 −17.1

105 −28.5

Reactants Intermediate Products

Figure 7.12
A schematic
diagram of how
enzymes facilitate
the formation of
an intermediate
state of a reaction
by favoring
rearrangement of the
reactants into the
intermediate state.