Biomedical Engineering Reference
In-Depth Information
The SODs are ubiquitous metallo-enzymes in oxygen-tolerant organisms and protect
the organism against the toxic effects of O
2
•
by effi ciently catalyzing its dismuta-
tion into O
2
and H
2
O
2
via a cyclic oxidation-reduction electron transfer mechanism
as shown in Scheme 1, with Cu, Zn-SOD with an example. Two steps have been pro-
posed in the dismutation reaction, in which the oxidized form of the metal central ions
(i.e. Cu (II), Fe(III), Mn(III) for Cu, Zn-SOD, Fe-SOD and Mn-SOD, respectively)
were fi rst reduced to the reduced form (i.e. Cu (I), Fe(II), Mn(II) for Cu, Zn-SOD,
Fe-SOD and Mn-SOD, respectively) with the formation of O
2
followed by a subse-
quent equivalent oxidation of the reduced form of the metal ions into their oxidized
form by O
2
•
with the release of H
2
O
2
(Scheme 6.1) [98].
Valentine
et al.
demonstrated that Cu
2
ions are in the same site in native Cu,
Zn-SOD protein and CuESOD (E
empty, i.e. with removal of Zn ion from the native
Cu, Zn-SOD) and the activity of the CuESOD is at least 80
5% that of the native
Cu, Zn-SOD [99]. However, the EZnSOD (E
empty, i.e. with removal of Cu ion
from the native Cu, Zn-SOD) does not show any activity for catalytic dismutation of
O
2
•
. This suggests Cu
2
present in the Cu, Zn-SOD is essential for O
2
•
dismutation
even though Zn
2
is also required for dismutase activity [100-102].
The structures of the SODs (i.e. Cu, Zn-SOD, Fe-SOD, and Mn-SOD) in the SOD
family are known to be relatively different. For instance, the Cu, Zn-SOD, which is the
fi rst SOD characterized and analyzed by X-ray methods [103], is a homodimer with a
molecular weight of 31 200 Da and containing one Cu (II) and Zn (II) per monomer
subunit. Its fundamental structural motif is a
-barrel. In the Cu, Zn-SOD, the met-
als are bound by sequences connecting the barrel strands and are on opposite sides of
the dimer with the Cu atoms separated by 33.8 Å. The dimer is an elongated ellipsoid
about 33 Å wide, 67 Å long and 36 Å deep [103].
The second family of SODs, which utilizes either Fe or Mn to catalyze the dismu-
tation of O
2
•
(i.e. Fe-SOD and Mn-SOD), constitutes a close-knit group of proteins
in which the sequences are highly conserved [104, 105]. Fe-SOD and Mn-SOD have
been isolated as either dimers or tetramers [67]. Crystallographic analyses of both
β
SOD
2 O
2
•
2H
O
2
H
2
O
2
SOD (Cu
)
O
2
O
2
•
SOD (Cu
2
)
O
2
•
H
2
O
2
SCHEME 1
Schematic illustration of the biological process of O
2
•
dismutation into O
2
and H
2
O
2
catalyzed
by Cu, Zn-SOD via a cyclic oxidation-reduction electron transfer mechanism. (Reprinted from [98], with per-
mission from Elsevier.)
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