Chemistry Reference
In-Depth Information
a range of redox potential from less than 200 mV to at least 800 mV. One of the challenges for the future will be to
determine what programmes this fine-tuning of redox properties of type 1 copper centres.
COPPER-CONTAINING ENZYMES IN OXYGEN ACTIVATION AND REDUCTION
There has been enormous activity in the field of Cu(I)-dioxygen chemistry in the last 25 years, with our
information coming from both biochemical/biophysical studies and to a very important extent from coordi-
nation chemistry. This has resulted in the structural and spectroscopic characterisation of a large number of
Cu dioxygen complexes, some of which are represented in
Figure 14.3
(
Himes and Karlin, 2009
). The
µ-1,2-peroxo-Cu
2
II
2
:
2
-peroxo-Cu
2
II
bis-µ-oxo-Cu
2
II
µ-
η
η
2+
2+
O
2+
O
Cu
II
O
Cu
II
Cu
II
Cu
III
Cu
III
Cu
II
O
O
electrophilic
O
nucleophilic
aromatic hydroxylation
H abstraction
1
side-on,
2
superoxo-Cu
II
end-on,
2
peroxo-Cu
III
1
end-on,
η
η
η
end-on,
η
superoxo
hydroperoxo
1+
1+
1+
1+
O
O
Cu
II
O
Cu
II
O
Cu
II
Cu
III
OH
O
O
O
electrophilic ?
FIGURE 14.3
Crystallographically or spectroscopically characterised Cu
O
2
adduct structures found in small molecule ligand
Cu
e
e
complexes, with characteristic reactivity patterns (green). (Adapted from
Himes & Karlin, 2009
.)
O
2
-reactive centres in Cu enzymes can be either mononuclear (type 2), dinuclear (type 3), or trinuclear (Type
2 and 3). We will discuss each in turn: the trinuclear sites will be included in our discussion of multicopper
oxidases.
Type 2 Copper Proteins
A number of X-ray structures are available for oxidases and oxygenases containing Type 2 copper sites including
amine oxidases, galactose oxidase, lysyl oxidase, dopamine
-hydroxylating
monooxygenase. However, there is a paradox concerning type 2 mononuclear Cu sites which bind dioxygen.
In order to activate O
2
, unless they go to the unlikely Cu(III) state, they cannot supply the 2nd electron which is
required to convert the cupric-superoxo complex to the more likely oxygen donor, the cupric-peroxo complex.
There are two possible solutions to this dilemma.
The first is best illustrated by galactose oxidase which converts galactose
b
-hydroxylase, and peptidyl-glycine
a
þ
O
2
to the corresponding
aldehyde
H
2
O
2
. Originally this enzyme was thought to involve Cu(III). However, galactose oxidase turns out to
be a free radical metalloenzyme (
Rogers and Dooley, 2003
)
and solves the problem via a novel metallo-radical
complex comprising a tyrosine radical coordinated to a Cu ion in the active site (
Figure 14.4
)
. The unusually stable
þ
