| Title |
Reactions of plasmodium falciparum type II NADH: ubiquinone oxidoreductase with nonphysiological quinoidal and nitroaromatic oxidants / |
| Authors |
Misevičienė, Lina ; Golinelli-Cohen, Marie-Pierre ; Kairys, Visvaldas ; Marozienė, Audronė ; Lesanavičius, Mindaugas ; Čėnas, Narimantas |
| DOI |
10.3390/ijms26062509 |
| Full Text |
|
| Is Part of |
International journal of molecular sciences.. Basel : MDPI. 2025, vol. 26, iss. 6, art. no. 2509, p. [1-16].. ISSN 1661-6596. eISSN 1422-0067 |
| Keywords [eng] |
type II NADH:ubiquinone oxidoreductase ; Plasmodium falciparum ; quinones ; nitroaromatic compounds ; reduction mechanism |
| Abstract [eng] |
In order to detail the antiplasmodial effects of quinones (Q) and nitroaromatic compounds (ArNO2), we investigated their reduction mechanism by Plasmodium falciparum flavoenzyme type II NADH:ubiquinone oxidoreductase (PfNDH2). The reactivity of Q and ArNO2 (n = 29) follows a common trend and exhibits a parabolic dependence on their single-electron reduction potential (E71), albeit with significantly scattered data. The reactivity of quinones with similar E71 values increases with their lipophilicity. Quinones are reduced by PfNDH2 in a two-electron way, but ArNO2 are reduced in a single-electron way. The inhibition studies using NAD+ and ADP-ribose showed that quinones oxidize the complexes of reduced enzyme with NADH and NAD+. This suggests that, as in the case of other NDH2s, quinones and the nicotinamide ring of NAD(H) bind at separate sites. A scheme of PfNDH2 catalysis is proposed, consistent with both the observed ‘ping-pong’ mechanism and the presence of two substrate binding sites. Molecular docking showed that Q and ArNO2 bind in a similar manner and that lipophilic quinones have a higher affinity for the binding site. One may expect that PfNDH2 can be partially responsible for the previously observed enhanced antiplasmodial activity of aziridinylbenzoquinones caused by their two-electron reduction, as well as for the redox cycling and oxidative stress-type action of ArNO2. |
| Published |
Basel : MDPI |
| Type |
Journal article |
| Language |
English |
| Publication date |
2025 |
| CC license |
|
