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140 Chapter 6
glutathione called trypanothione in which the C-terminal glycine carboxylates
are connected by a spermidine linker, as shown in Figure 6.25.
Examination of the amino acid sequence of the Trypanosoma congolense
enzyme revealed that three of the amino acid residues involved in substrate
binding in human glutathione reductase are modiWed in the parasite enzyme:
Arg-347 (found as alanine in TR), Ala-34 (found as glutamine in TR) and Arg-
37 (found as tryptophan in TR). The location of these residues is shown
in Figure 6.26. Mutation of these three residues in the parasite TR to the
CO −
2 O
CO −
H
H
2 O
H
H
H 3 N + N
N
+
N
N
N
H
H
3 N
N
H
O
O + trypanothione
O
O +
S
H 2 N reductase
HS
H 2 N
S
FAD
SH
O
O
H
NADPH NADP + O
O
H
H 3 N
N
+ N
N
H 3 N N
+
N N
H
H
−
H H
CO 2 O
CO −
2 O
oxidised trypanothione
Figure 6.25 Trypanothione reductase.
reduced trypanothione
Figure 6.26 Location of Arg-347, Ala-34 and Arg-37 (red, right hand side) in glutathione reductase
active site, in relation to reduced glutathione (black), FAD (black, top) and Cys 41/46 (red, balland-stick).
Picture prepared using RASMOL.