Biology Reference
In-Depth Information
“reaction coordinate” representing the progression of the binding process (e.g., in
terms of intermolecular distances), and the
y
-axis represents the Gibbs free energy
level, G, of the system along the reaction coordinate. The binding processes can be
divided into three classes depending on the signs of the associated Gibbs free
energy changes - (1) Type I (also called
downhill
or
exergonic
) when
D
<
G
0,
D
¼
(2) Type II (also called “equilibrium”) when
G
0, and (3) Type III (also called
uphill
or
endergonic
) when
D
>
0.
Due to the positivity (i.e., the positive sign) of
G
G, Type III binding processes
cannot occur spontaneously, that is, L cannot bind to P to form L'
∙
P' to any great
extent. However, there are two ways to increase the extent of the binding process
so as to increase the concentration of the L'
D
P' complex - (1) By utilizing
the concentration effect (discussed above), that is, by increasing [L] and [P],
and (2) By utilizing the structural effect, that is., by increasing the binding
affinities of L and P by modifying their structures either
non-covalently
(e.g.,
through allosteric ligand) or
covalently
(e.g.,
through transcription or posttran-
scriptionally
via phosphorylation or acetylation [Zhaio et al. 2010; Wang et al.
2010]).
As indicated in Eq.
7.3
, the concentration effect is
global
, affecting all
interacting molecules more or less simultaneously due to the rapidity of diffusion
processes, whereas the structural effect can be
local
since structural changes can
be made only to select molecules by enzyme catalyzed posttranscriptional modifi-
cation or transcriptional activation of select genes. Because of these two
mechanisms, ligand-binding processes can be regulated in two contrasting and
independent ways -
local
and
global
and fast and slow - the extra degrees of
freedom introduced by these processes may have played important roles in
biological evolution.
What distinguishes
chemical
and
biochemical reactions
is that the former
depends on
molecular collisions among reactants
while the latter depends on
molecular binding to proteins
. When two molecules A and B collide, they typically
remain in physical contact only transiently (typically lasting for 10
13
-10
15
s, the
periods of bond vibrations). In contrast, when a ligand bind to a protein, the ligand-
protein complex can last for much longer times, depending on the geometry of the
binding pocket of the protein which determines the activation free energy barrier
for the de-binding of the ligand. Whether or not the colliding molecules, A and B,
will undergo chemical reactions critically depends on the magnitude and the
direction of the momentum changes experienced by the colliding molecules, the
momentum p of a particle being defined as the mass m of the particle times its
velocity v, that is, p
∙
mv. When A and B collide with a sufficient momenta in the
right direction, the collision can lead to chemical transformations. Whether or not
the binding of a ligand L to a protein P will lead to a chemical transformation (i.e.,
enzymic catalysis) depends on two factors - (1) the thermodynamic factor requiring
that the “binding free energy,”
¼
G, in Table
7.1
, be negative, and (2) the kinetic
factor dictating that the activation free energy,
D
G
{
, is small enough to be overcome
by thermal fluctuations of enzymes (Ji 1974a, 1979).
D
