Denaturation of Protein by Chlorine Dioxide: Oxidative Modification of Tryptophan and Tyrosine Residues†
View
Author Information
Cite this: Biochemistry 2007,
46, 16, 4898–4911
Publication
Date:March 31, 2007
https://doi.org/10.1021/bi061827u
Copyright
© 2007 American Chemical Society
Art
Norio Ogata 1DOI: 10.1021/bi061827u
Abstract
Oxychlorine compounds, such as hypochlorous acid
(HOCl) and chlorine dioxide (ClO2), have potent antimicrobial activity.
Although the biochemical mechanism of the antimicrobial activity of HOCl has
been extensively investigated, little is known about that of ClO2. Using bovine
serum albumin and glucose-6-phosphate dehydrogenase of Saccharomyces cerevisiae
as model proteins, here I demonstrate that the antimicrobial activity of ClO2
is attributable primarily to its protein-denaturing activity. By solubility analysis,
circular dichroism spectroscopy, differential scanning calorimetry, and
measurement of enzymatic activity, I demonstrate that protein is rapidly
denatured by ClO2 with a concomitant decrease in the concentration of ClO2 in
the reaction mixture. Circular dichroism spectra of the ClO2-treated proteins
show a change in ellipticity at 220 nm, indicating a decrease in alpha-helical
content. Differential scanning calorimetry shows that transition temperature
and endothermic transition enthalpy of heat-induced unfolding decrease in the
ClO2-treated protein. The enzymatic activity of glucose-6-phosphate
dehydrogenase decreases to 10% within 15 s of treatment with 10 microM ClO2.
Elemental analyses show that oxygen, but not chlorine, atoms are incorporated in
the ClO2-treated protein, providing direct evidence that protein is oxidized by
ClO2. Furthermore, mass spectrometry and nuclear magnetic resonance
spectroscopy show that tryptophan residues become N-formylkynurenine and
tyrosine residues become 3,4-dihydroxyphenylalanine (DOPA) or
2,4,5-trihydroxyphenylalanine (TOPA) in the ClO2-treated proteins. Taking these
results together, I conclude that microbes are inactivated by ClO2 owing to
denaturation of constituent proteins critical to their integrity and/or
function, and that this denaturation is caused primarily by covalent oxidative
modification of their tryptophan and tyrosine residues.
Similar
articles
Stewart DJ, Napolitano MJ,
Bakhmutova-Albert EV, Margerum DW.Inorg Chem. 2008 Mar 3;47(5):1639-47.
doi: 10.1021/ic701761p. Epub 2008 Feb 7.PMID: 18254588
Napolitano MJ, Green BJ, Nicoson JS,
Margerum DW.Chem Res Toxicol. 2005 Mar;18(3):501-8. doi: 10.1021/tx049697i.PMID: 15777090
Ison A, Odeh IN, Margerum DW.Inorg Chem. 2006 Oct
16;45(21):8768-75. doi: 10.1021/ic0609554.PMID: 17029389
Wei M, Lai J, Zhan P.Wei Sheng Wu Xue Bao.
2012 Apr 4;52(4):429-34.PMID: 22799207 Review. Chinese.
Fukayama MY, Tan H, Wheeler WB, Wei CI.Environ Health
Perspect. 1986 Nov;69:267-74. doi: 10.1289/ehp.8669267.PMID: 3545804 Free PMC article. Review.
Cited
by 16 articles
Augustyn W, Chruściel A, Hreczuch W,
Kalka J, Tarka P, Kierat W.Int J Environ Res Public Health. 2022 Jan
10;19(2):750. doi: 10.3390/ijerph19020750.PMID: 35055571 Free PMC article. Review.
Foladori P, Cutrupi F, Cadonna M, Manara
S.Environ Res. 2022 May 1;207:112204. doi: 10.1016/j.envres.2021.112204. Epub
2021 Oct 14.PMID: 34656637 Free PMC article. Review.
Hatanaka N, Xu B, Yasugi M, Morino H,
Tagishi H, Miura T, Shibata T, Yamasaki S.J Hosp Infect. 2021 Dec;118:20-26. doi:
10.1016/j.jhin.2021.09.006. Epub 2021 Sep 15.PMID: 34536532 Free PMC article.
Andreu S, Ripa I, Bello-Morales R,
López-Guerrero JA.Viruses. 2021 Mar 23;13(3):531. doi: 10.3390/v13030531.PMID: 33807081 Free PMC article.
Ge Y, Zhang X, Shu L, Yang X.Bull Environ Contam
Toxicol. 2021 Apr;106(4):560-567. doi: 10.1007/s00128-021-03137-3. Epub 2021
Feb 25.PMID: 33629148 Free PMC article. Review.
Keine Kommentare:
Kommentar veröffentlichen