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Enzymatic Redox Chemistry 141
corresponding residues in the human glutathione reductase gave a mutant
enzyme with 10 3 -fold lower trypanothione reductase activity and 10 4 -fold
higher glutathione reductase activity. The speciWcity of the parasite enzyme
for trypanothione over glutathione oVers the potential for selective anti-parasite
activity via inhibition of trypanothione reductase.
6.6 Deazaflavins and pterins
Nicotinamide and riboXavin are by far the most common carbon-based redox
cofactors used by enzymes, but there are several other heterocyclic redox
cofactors used by particular enzymes.
Factor F 420 was isolated in 1978 from methanogenic bacteria (strictly anaerobic
bacteria which ferment acetate to methane and carbon dioxide) in yields
of up to 100 mg per kg of cells. It was found to have a structure similar to that
of riboXavin, except that N-5 is replaced by a carbon atom. The discovery of
this deazaXavin prompted an investigation into the properties of other deazaanalogues
of riboXavin, which are shown in Figure 6.27. Both factor F 420 and
5-deazaXavin have much lower redox potentials than riboXavin itself, but
Flavin
5-Deazaflavin
R
N
N
R
N
N
O
N
O
NH
O
NH
E 0
−210 mV
−310 mV
Redox chemistry
1e − and 2e −
2e − only
1-Deazaflavin
R
N
N
O
O
NH
O
−280 mV
1e − and 2e −
Factor F 420
HO
HO
N
OH
OH
N
O
O
O
P O
O−
O
N
H
CO 2
−
O
H
N
CO 2
−
CO 2
−
NH
−360 mV
2e − only
O
Figure 6.27 Structures and redox potentials of natural and synthetic deazaXavins.