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Kinetics of formation and reactivity of the persulfide in the one-cysteine peroxiredoxin from Mycobacterium tuberculosis.
J Biol Chem. 2019 09 13; 294(37):13593-13605.JB

Abstract

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) × 103 m-1 s-1 (pH 7.4, 25 °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 pKa 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.

Authors+Show Affiliations

Laboratorio de Enzimología, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay ecuevasanta@fcien.edu.uy. Unidad de Bioquímica Analítica, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay.Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay marceloreyes@fmed.edu.uy. Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay. Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay. Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay. Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay. Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.Laboratorio de Enzimología, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay.Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay. Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31311857

Citation

Cuevasanta, Ernesto, et al. "Kinetics of Formation and Reactivity of the Persulfide in the One-cysteine Peroxiredoxin From Mycobacterium Tuberculosis." The Journal of Biological Chemistry, vol. 294, no. 37, 2019, pp. 13593-13605.
Cuevasanta E, Reyes AM, Zeida A, et al. Kinetics of formation and reactivity of the persulfide in the one-cysteine peroxiredoxin from Mycobacterium tuberculosis. J Biol Chem. 2019;294(37):13593-13605.
Cuevasanta, E., Reyes, A. M., Zeida, A., Mastrogiovanni, M., De Armas, M. I., Radi, R., Alvarez, B., & Trujillo, M. (2019). Kinetics of formation and reactivity of the persulfide in the one-cysteine peroxiredoxin from Mycobacterium tuberculosis. The Journal of Biological Chemistry, 294(37), 13593-13605. https://doi.org/10.1074/jbc.RA119.008883
Cuevasanta E, et al. Kinetics of Formation and Reactivity of the Persulfide in the One-cysteine Peroxiredoxin From Mycobacterium Tuberculosis. J Biol Chem. 2019 09 13;294(37):13593-13605. PubMed PMID: 31311857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kinetics of formation and reactivity of the persulfide in the one-cysteine peroxiredoxin from Mycobacterium tuberculosis. AU - Cuevasanta,Ernesto, AU - Reyes,Aníbal M, AU - Zeida,Ari, AU - Mastrogiovanni,Mauricio, AU - De Armas,María Inés, AU - Radi,Rafael, AU - Alvarez,Beatriz, AU - Trujillo,Madia, Y1 - 2019/07/16/ PY - 2019/04/12/received PY - 2019/07/12/revised PY - 2019/7/18/pubmed PY - 2020/5/19/medline PY - 2019/7/18/entrez KW - Mycobacterium tuberculosis KW - alkyl hydroperoxide reductase E KW - antioxidant KW - enzyme kinetics KW - hydrodisulfide KW - hydrogen sulfide KW - peroxiredoxin KW - persulfide KW - signaling compound KW - sulfenic acid SP - 13593 EP - 13605 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 294 IS - 37 N2 - 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) × 103 m-1 s-1 (pH 7.4, 25 °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 pKa 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/31311857/Kinetics_of_formation_and_reactivity_of_the_persulfide_in_the_one_cysteine_peroxiredoxin_from_Mycobacterium_tuberculosis_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=31311857 DB - PRIME DP - Unbound Medicine ER -