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. 2024 Feb 22;13(3):267.
doi: 10.3390/antiox13030267.

Cysteine Is the Only Universally Affected and Disfavored Proteomic Amino Acid under Oxidative Conditions in Animals

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Cysteine Is the Only Universally Affected and Disfavored Proteomic Amino Acid under Oxidative Conditions in Animals

Mario Schindeldecker et al. Antioxidants (Basel). .

Abstract

Oxidative modifications of amino acid side chains in proteins are a hallmark of oxidative stress, and they are usually regarded as structural damage. However, amino acid oxidation may also have a protective effect and may serve regulatory or structural purposes. Here, we have attempted to characterize the global redox role of the 20 proteinogenic amino acids in animals by analyzing their usage frequency in 5 plausible evolutionary paradigms of increased oxidative burden: (i) peroxisomal proteins versus all proteins, (ii) mitochondrial proteins versus all proteins, (iii) mitochondrially encoded respiratory chain proteins versus all mitochondrial proteins, (iv) proteins from long-lived animals versus those from short-lived animals, and (v) proteins from aerobic, free-living animals versus those from facultatively anaerobic animals. We have found that avoidance of cysteine in the oxidative condition was the most pronounced and significant variation in the majority of comparisons. Beyond this preeminent pattern, only local signals were observed, primarily increases in methionine and glutamine as well as decreases in serine and proline. Hence, certain types of cysteine oxidation appear to enforce its proteome-wide evolutionary avoidance despite its essential role in disulfide bond formation and metal ligation. The susceptibility to oxidation of all other amino acids appears to be generally unproblematic, and sometimes advantageous.

Keywords: ageing; free radical; one-electron oxidation; peroxidation; protein oxidation; thiyl radical.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Graphical representation of the factorial accumulation (positive values, green color) or depletion (negative values, red color) of each amino acid in paradigms I, II and III. Each of the 20 investigated animal species in these paradigms is represented by a single line within every 20-line stack per amino acid. Animals were sorted by decreasing longevity from left to right, as per Table 1 (i.e., from Homo sapiens, left, to Caenorhabditis elegans, right).

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