Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

248 Chapter 11
H H*
+ H
+
H 3 N
CO −
H 2 3 N
N
N
H
CO −
2
N
H
− CO 2
2− O 3 PO
OH
Ado CH 2
N
2− O 3 PO
OH
Ado CH 3
N
Ado CH 3
+
H 3 N
2− O 3 PO
OH
+
N
H
+
H
+
H
Ado CH 2
Ado CH 2
+
H 3 N
*H H
CO −
2
H NH
+ 3
+
H 3 N
2− O 3 PO
+
N
H
*H H
CO −
2
N
OH
+
H 3 N
2− O 3 PO
+
N
H
H
H
− CO 2
N
OH
Figure 11.12 Catalytic mechanism for lysine 2,3-aminomutase.
Fragmentation of the other C2N bond then gives a C-2 radical, which reacquires
a hydrogen atom to give the b-lysine-PLP adduct, as shown in Figure
11.12. What species is responsible for hydrogen atom abstraction By analogy
with the vitamin B 12 -dependent reactions, the reactive species is thought to be a
5 0 -deoxyadenosyl radical, formed by reductive cleavage C2S bond cleavage of
SAM. Generation of this radical species must be carried out by the [4Fe4S]
cluster, but the precise mechanism is of interest, since the C2S bond is much
stronger than the C2Co bond of vitamin B 12 . It is known that the a-amino and
carboxyl substituents of SAM are co-ordinated to the [4Fe4S] cluster, thus a
mechanism for activation can be drawn, as shown in Figure 11.13.
+ H 3 C
+
S
EnzS
H 2
Fe S N
S Fe
S Fe
Fe S
O
EnzS SEnz
O
OH OH
O
Ad
H
H 2 C
2+ H 3 C
S
EnzS
H 2
Fe S N
S Fe
S Fe
Fe S
O
EnzS SEnz
Figure 11.13 Generation of 5 0 -deoxyadenosyl radical from SAM by [4Fe4S] cluster.
O
Ad
OH OH
H
O