Chemistry Reference
In-Depth Information
(a)
(b)
(c)
FAD
FAD
Oxaloacetate
Fumarate
12.3 Å
[2Fe2S]
12.5 Å
[2Fe2S]
10.9 Å
11.0 Å
[4Fe4S]
[4Fe4S]
9.1 Å
9.1 Å
[3Fe4S]
[3Fe4S]
8.2 Å
17.4 Å
Q
P
B
P
25.1 Å
15.6 Å
B
D
Q
D
FIGURE 13.17
(a) Polypeptide fold; (b) electron transfer distances in E. coli quinol-fumarate reductase; and (c) inter-cofactor distances in
the W. succinogenes enzyme.
(From Iverson et al., 2002. Reproduced by permission of American Society for Biochemistry and Molecular
Biology. Copyright 2002.)
both the amino and carboxylate group of SAM. An electron is then transferred from the low potential reduced
cluster onto SAM generating the adenosyl radical and possibly also coordinating the liberated thiolate. The
binding of the liberated sulfur atom to the remaining coordination site of the iron may help to drive the ener-
getically unfavourable electron transfer step. The highly reactive 5
0
-deoxyadenosyl radical then initiates the
enzyme reaction by abstracting a hydrogen atom from the substrate RH to generate the free radical R
and
5
0
-deoxyadenosine. These radical SAM enzymes, as they are now called, constitute a large family involved in
many metabolic pathways, including biotin synthase and lipoate synthase. These enzymes catalyse the insertion of
sulfur atoms into aliphatic substrates. After activation of the organic substrate by the adenosyl radical, a second
Fe
S cluster is the source of the sulfur atoms for insertion into the dethioprecursor.
Finally, we remind our reader that in its apoform, cytoplasmic aconitase is active as an iron regulatory protein
(Chapter 8), binding to iron regulatory elements in the mRNAs of ferritin and transferrin receptor and regulating
their translation.
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