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Oxidant-Mediated Protein Amino Acid Conversion

Biological oxidation plays important roles in the pathogenesis of various diseases and aging. Carbonylation is one mode of protein oxidation. It has been reported that amino acids that are susceptible to carbonylation are arginine (Arg), proline (Pro), lysine, and threonine residues. The carbonylati...

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Autor principal: Suzuki, Yuichiro J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406366/
https://www.ncbi.nlm.nih.gov/pubmed/30823521
http://dx.doi.org/10.3390/antiox8020050
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author Suzuki, Yuichiro J.
author_facet Suzuki, Yuichiro J.
author_sort Suzuki, Yuichiro J.
collection PubMed
description Biological oxidation plays important roles in the pathogenesis of various diseases and aging. Carbonylation is one mode of protein oxidation. It has been reported that amino acids that are susceptible to carbonylation are arginine (Arg), proline (Pro), lysine, and threonine residues. The carbonylation product of both Arg and Pro residues is glutamyl semialdehyde. While chemically the oxidation reactions of neither Pro to glutamyl semialdehyde nor Arg to glutamyl semialdehyde are reversible, experimental results from our laboratory suggest that the biological system may drive the reduction of glutamyl semialdehyde to Pro in the protein structure. Further, glutamyl semialdehyde can be oxidized to become glutamic acid (Glu). Therefore, I hypothesize that biological oxidation post-translationally converts Arg to Pro, Arg to Glu, and Pro to Glu within the protein structure. Our mass spectrometry experiments provided evidence that, in human cells, 5–10% of peroxiredoxin 6 protein molecules have Pro-45 replaced by Glu. This concept of protein amino acid conversion challenges the dogma that amino acid sequences are strictly defined by nucleic acid sequences. I propose that, in the biological system, amino acid replacements can occur post-translationally through redox regulation, and protein molecules with non-DNA coding sequences confer functions.
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spelling pubmed-64063662019-03-08 Oxidant-Mediated Protein Amino Acid Conversion Suzuki, Yuichiro J. Antioxidants (Basel) Review Biological oxidation plays important roles in the pathogenesis of various diseases and aging. Carbonylation is one mode of protein oxidation. It has been reported that amino acids that are susceptible to carbonylation are arginine (Arg), proline (Pro), lysine, and threonine residues. The carbonylation product of both Arg and Pro residues is glutamyl semialdehyde. While chemically the oxidation reactions of neither Pro to glutamyl semialdehyde nor Arg to glutamyl semialdehyde are reversible, experimental results from our laboratory suggest that the biological system may drive the reduction of glutamyl semialdehyde to Pro in the protein structure. Further, glutamyl semialdehyde can be oxidized to become glutamic acid (Glu). Therefore, I hypothesize that biological oxidation post-translationally converts Arg to Pro, Arg to Glu, and Pro to Glu within the protein structure. Our mass spectrometry experiments provided evidence that, in human cells, 5–10% of peroxiredoxin 6 protein molecules have Pro-45 replaced by Glu. This concept of protein amino acid conversion challenges the dogma that amino acid sequences are strictly defined by nucleic acid sequences. I propose that, in the biological system, amino acid replacements can occur post-translationally through redox regulation, and protein molecules with non-DNA coding sequences confer functions. MDPI 2019-02-25 /pmc/articles/PMC6406366/ /pubmed/30823521 http://dx.doi.org/10.3390/antiox8020050 Text en © 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Suzuki, Yuichiro J.
Oxidant-Mediated Protein Amino Acid Conversion
title Oxidant-Mediated Protein Amino Acid Conversion
title_full Oxidant-Mediated Protein Amino Acid Conversion
title_fullStr Oxidant-Mediated Protein Amino Acid Conversion
title_full_unstemmed Oxidant-Mediated Protein Amino Acid Conversion
title_short Oxidant-Mediated Protein Amino Acid Conversion
title_sort oxidant-mediated protein amino acid conversion
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406366/
https://www.ncbi.nlm.nih.gov/pubmed/30823521
http://dx.doi.org/10.3390/antiox8020050
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