6
Bioorganic Chemistry
O
O
N
1
P
O
O
O
OH
O
O
N
2
OH
P
O
O
O
P
O
O
O
P
O
O
O
O
O
N
1
P
O
O
O
O
O
O
N
2
OH
P
O
O
P
O
O
O
P
O
O
O
O
O
O
N
1
P
O
O
O
O
O
O
N
2
OH
P
O
O
O
P
O
O
O
P
O
O
O
+
O
O
N
OH
P
O
O
O
P
O
O
O
P
O
O
O
ROH
O
O
N
OH
P
O
O
O
P
O
O
O
P
O
O
RO
O
O
O
N
OH
P
O
O
O
P
O
O
O
O
P
O
O
RO
+
(a)
(b)
Fig. 4
(a) Polynucleotide biosynthesis. (b) Nucleophile phosphorylation with ATP.
transfer phosphate groups to nucleophiles
like the hydroxyl groups of glucose dur-
ing glucose metabolism. In this case, the
nucleophile will add to the gamma or
terminal phosphate, and the leaving group
will be adenosine diphosphate, ADP, not
pyrophosphate.
2.2
Noncovalent Interactions
We now turn our attention to the realm of
noncovalent interactions, those forces that
cause molecules to associate with and rec-
ognize each other. These interactions are
of importance in all of biochemistry, from
the speciFc hydrogen bonding patterns in
the base pairs of DNA that allow for in-
formation to be coded to the enzymes’
ability to distinguish between two ligands
that can differ by a single methyl group.
In addition to aiding in the understanding
of binding processes, these forces are of
key importance in the realm of catalysis
as well. This concept will be explored at
greater length later.
The hypothetical binding process of a
protein ‘‘P’’ and a ligand ‘‘L,’’ forming
a complex PL can be described by a
simple equilibrium (±ig. 5). The equilib-
rium association constant
K
a
=
[PL]/[P][L]
is related to the standard free energy
of binding (
1
G
bind
)th
roughtheexp
re
s
-
sion
1
G
bind
=−
R
T
ln
K
a
(where R is the
universal gas constant and
T
is the tem-
perature). This
1
G
bind
in turn is the sum
of many factors such as coulombic at-
tractions, hydrogen bonding, hydrophobic
effects, van der Waals’ forces, conforma-
tional effects, and translational/rotational
entropy. A good rule of thumb is that for
every 1.4 kcal mol
1
increase in
1
G
bind
,
there is a tenfold increase in binding afFn-
ity.
1
G
bind
being a free energy, which
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