Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 294, Issue 37, Pages 13593-13605Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA119.008883
Keywords
hydrogen sulfide; Mycobacterium tuberculosis; peroxiredoxin; antioxidant; enzyme kinetics; alkyl hydroperoxide reductase E; hydrodisulfide; persulfide; signaling compound; sulfenic acid
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Funding
- Comision Sectorial de Investigacion Cientifica (CSIC)
- CSIC I + [D2016]
- Fondo Vaz Ferreira MEC
- PEDECIBA
- Comision Academica de Posgrado (CAP, Universidad de la Republica)
- Programa de Desarrollo de las Ciencias Basicas (PEDECIBA, Uruguay)
- Agencia Nacional de Investigacion e Innovacion (ANII)
- Universidad de la Republica
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Hydrogen sulfide (H2S) participates in prokaryotic metabolism and is associated with several physiological functions in mammals. H2S reacts with oxidized thiol derivatives (i.e. disulfides and sulfenic acids) and thereby forms persulfides, which are plausible transducers of the H2S-mediated signaling effects. The one-cysteine peroxiredoxin alkyl hydroperoxide reductase E from Mycobacterium tuberculosis (MtAhpE-SH) reacts fast with hydroperoxides, forming a stable sulfenic acid (MtAhpE-SOH), which we chose here as a model to study the interactions between H2S and peroxiredoxins (Prx). MtAhpE-SOH reacted with H2S, forming a persulfide (MtAhpE-SSH) detectable by mass spectrometry. The rate constant for this reaction was (1.4 +/- 0.2) x 10(3) M-1 s(-1) (pH 7.4, 25 degrees C), six times higher than that reported for the reaction with the main low-molecular-weight thiol in M. tuberculosis, mycothiol. H2S was able to complete the catalytic cycle of MtAhpE and, according to kinetic considerations, it could represent an alternative substrate in M. tuberculosis. MtAhpE-SSH reacted 43 times faster than did MtAhpE-SH with the unspecific electrophile 4,4 '-dithiodipyridine, a disulfide that exhibits no preferential reactivity with peroxidatic cysteines, but MtAhpE-SSH was less reactive toward specific Prx substrates such as hydrogen peroxide and peroxynitrite. According to molecular dynamics simulations, this loss of specific reactivity could be explained by alterations in the MtAhpE active site. MtAhpE-SSH could transfer its sulfane sulfur to a low-molecular-weight thiol, a process likely facilitated by the low pK(a) of the leaving thiol MtAhpE-SH, highlighting the possibility that Prx participates in transpersulfidation. The findings of our study contribute to the understanding of persulfide formation and reactivity.
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