Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: KEGG:D02011 (
FAD
)
5,530
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ferredoxin:NADP
+
oxidoreductase from
Plasmodium falciparum
(
Pf
FNR) catalyzes the NADPH-dependent reduction of ferredoxin (
Pf
Fd), which provides redox equivalents for the biosynthesis of isoprenoids and fatty acids in the apicoplast. Like other flavin-dependent electrontransferases,
Pf
FNR is a potential source of free radicals of quinones and other redox cycling compounds. We report here a kinetic study of the reduction of quinones, nitroaromatic compounds and aromatic
N-
oxides by
Pf
FNR
.
We show that all these groups of compounds are reduced in a single-electron pathway, their reactivity increasing with the increase in their single-electron reduction midpoint potential (
E
1
7
). The reactivity of nitroaromatics is lower than that of quinones and aromatic
N
-oxides, which is in line with the differences in their electron self-exchange rate constants.
Quinone
reduction proceeds via a ping-pong mechanism. During the reoxidation of reduced
FAD
by quinones, the oxidation of FADH
.
to
FAD
is the possible rate-limiting step. The calculated electron transfer distances in the reaction of
Pf
FNR with various electron acceptors are similar to those of
Anabaena
FNR, thus demonstrating their similar "intrinsic" reactivity. Ferredoxin stimulated quinone- and nitro-reductase reactions of
Pf
FNR, evidently providing an additional reduction pathway via reduced
Pf
Fd. Based on the available data,
Pf
FNR and possibly
Pf
Fd may play a central role in the reductive activation of quinones, nitroaromatics and aromatic
N-
oxides in
P. falciparum,
contributing to their antiplasmodial action.
...
PMID:Reactions of
Plasmodium falciparum
Ferredoxin:NADP
+
Oxidoreductase with Redox Cycling Xenobiotics: A Mechanistic Study. 3237 Mar 3
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