2022
DOI: 10.3390/ijms23158371
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First Experimental Evidence for Reversibility of Ammonia Loss from Asparagine

Abstract: Ammonia loss from ʟ-asparaginyls is a nonenzymatic reaction spontaneously occurring in all proteins and eventually resulting in damaging isoaspartate residues that hamper protein function and induce proteinopathy related to aging. Here, we discuss theoretical considerations supporting the possibility of a full repair reaction and present the first experimental evidence of its existence. If confirmed, the true repair of ʟ-asparaginyl deamidation could open new avenues for preventing aging and neurodegenerative … Show more

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Cited by 2 publications
(3 citation statements)
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“…There is a negative relationship between the asparagine content and protein lifetime. However, some studies have suggested that spontaneous deamidation of asparagine generates an isoaspartate residue that hampers protein function and induces disorders associated with senescence [ 10 ]. Sequence- and structure-based methods can detect asparagine deamidation in proteins [ 11 ]; thus, we can predict the function of proteins through these methods.…”
Section: Introductionmentioning
confidence: 99%
“…There is a negative relationship between the asparagine content and protein lifetime. However, some studies have suggested that spontaneous deamidation of asparagine generates an isoaspartate residue that hampers protein function and induces disorders associated with senescence [ 10 ]. Sequence- and structure-based methods can detect asparagine deamidation in proteins [ 11 ]; thus, we can predict the function of proteins through these methods.…”
Section: Introductionmentioning
confidence: 99%
“…Besides reviewing the available theoretical , we reported the first experimental evidence on the reversibility of isoAsp via protein succinimide/ isoaspartate ammonia ligase (PSIAL) activity[7]. Such activity was found in e.g.…”
mentioning
confidence: 99%
“…Being intrigued by the apparently irreversible nature of deamidation that seems to be in stark contrast with observed cell self-renewal phenomena (e.g., totally normal “young” babies born by woman 60 and more years old), we investigated the possibility of true isoAsp-to-Asn repair. Besides reviewing the available theoretical arguments, we reported the first experimental evidence on the reversibility of isoAsp via protein succinimide/isoaspartate ammonia ligase (PSIAL) activity [ 7 ]. Such activity was found in e.g.…”
mentioning
confidence: 99%