REDOX PROPERTIES OF CHLOROBACULUM TEPIDUM FERREDOXIN:NADP+ OXIDOREDUCTASE: POTENTIOMETRIC CHARACTERISTICS AND REACTIONS WITH PROOXIDANT XENOBIOTICS

Dominykas Laibakojis1, Daisuke Seo2, Mindaugas Lesanavičius1, Narimantas Čėnas1

1 Department of Xenobiotics Biochemistry, Institute of Biochemistry, Life Sciences Center, Vilnius University, Lithuania

2 Division of Materials Science, Graduate School of Natural Science and Technology, Kanazawa University, Japan

[email protected]

$ OXIDOREDUCTASE: POTENTIOMETRIC CHARACTERISTICS AND REACTIONS WITH PROOXIDANT XENOBIOTICS} {Chlorobaculum tepidum} ferredoxin:NADP\(^{+}\) oxidoreductase ({Ct}FNR) is a thioredoxin reductase (TrxR)-type FNR with scarcely characterized redox properties and reactivity with nonphysiological electron acceptors. The enzyme employs a noncovalently bound FAD and acts in transforming between one- and two-electron transfer with its native substrates NADP(H) and low molecular weight protein ferredoxin (Fd). The TrxR-type FNRs exhibit a homodimeric structure with their NADP(H)-binding domain being inserted between two segments of FAD-binding domains. The domains are mobile during catalysis, as the distance between the bound NADP(H) and FAD is ~15 Å, too great for efficient electron transfer [1,2].

In this study, we combined steady-state and presteady-state kinetic methods to examine the potentiometric characteristics of {Ct}FNR and its reactions with prooxidant xenobiotics. On the basis of redox reactions with 3-acetylpyridine adenine dinucleotide phosphate, the two-electron reduction midpoint potential of FAD cofactor was estimated to be −0.275 V, and photoreduction using 5-deazaFMN as a photosensitizer revealed that the difference in the redox potentials between the first and second single-electron transfer steps was 0.042 V. The enzymatic reaction proceeds via the {ping-pong} mechanism and exhibits the expected inhibition patterns by the reaction product NADP\(^{+}\), namely competitive inhibition towards NADPH and uncompetitive inhibition towards a quinone. The reactivity of quinones and nitroaromatics towards {Ct}FNR increases with their increasing single-electron reduction midpoint potentials; however, the reactivity of nitroaromatics was lower due to their lower electron self-exchange rate. The reduction reaction of quinones proceeds in a mixed single- and two-electron way, and nitroaromatics are reduced via the single-electron reaction. The experiments with varied ionic strength of the buffer exhibit a trend similar to that seen in other TrxR-type FNRs from {Bacillus subtilis} and {Rhodopseudomonas palustris}: the {k}\(_{cat}\)/{K}\(_{m}\) of a noncharged electron acceptor remains constant, while it increases for the negatively charged FeEDTA\(^{-}\) and decreases for the positively charged benzyl viologen upon increasing the ionic strength, thus giving insight into the role of charged amino acid residues in the vicinity of enzyme-bound FAD [3,4].

The obtained results are generally similar to those obtained with {Rp}FNR and {Bs}FNR and further expand our understanding of the novel TrxR-type FNRs and their catalysis.


[1] Hammerstad, M., Hersleth, H. P. (2021). Overview of structurally homologous flavoprotein oxidoreductases containing the low Mr thioredoxin reductase-like fold—A functionally diverse group. Arch. Biochem. Biophys., 702, 108826.

[2] Muraki, N., Seo, D., Shiba, T., Sakurai, T., Kurisu, G. (2010). Asymmetric dimeric structure of ferredoxin-NAD(P)+ oxidoreductase from the green sulfur bacterium Chlorobaculum tepidum: Implications for binding ferredoxin and NADP+. J. Mol. Biol., 401, 403–414.

[3] Lesanavičius, M., Seo, D., Čėnas, N. (2024). Thioredoxin Reductase-Type Ferredoxin: NADP+ Oxidoreductase of Rhodopseudomonas palustris: Potentiometric Characteristics and Reactions with Nonphysiological Oxidants. Antioxidants, 11(5), 1000.

[4] Lesanavičius, M., Seo, D., Maurutytė, G., Čėnas, N. (2024). Redox Properties of Bacillus subtilis Ferredoxin:NADP+ Oxidoreductase: Potentiometric Characteristics and Reactions with Pro-Oxidant Xenobiotics. Int. J. Mol. Sci., 25(10), 5373.