ArticleProceedings of the National Academy of Sciences of the United States of America1997
Deficiency of a protein-repair enzyme results in the accumulation of altered proteins, retardation of growth, and fatal seizures in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
98 citing papers in PubMed, 289 citations in OpenAlex.
- Potential roles of aspartic acid D-isomerization in proteins implicated in the pathogenesis of Alzheimer's disease.Neural regeneration research · 2026Article
- PCMT1 generates the C-terminal cyclic imide degron on CRBN substrates.Nature chemical biology · 2026Article
- Improved red blood cell storage quality of blood from donors carrying the hypermorphic PIMT I120 variant.HemaSphere · 2026Article
- Mammalian Tolerance to Amino Acid Heterochirality.Chembiochem : a European journal of chemical biology · 2025Review
- Immunotherapeutic targeting of aging-associated isoDGR motif in chronic lung inflammation.Aging cell · 2025Article
- Genesis and regulation of C-terminal cyclic imides from protein damage.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Isoaspartate formation and irreversible aggregation of collapsin response mediator protein 2: implications for the etiology of epilepsy and age-related cognitive decline.Research square · 2024Article
- Structural basis for FN3K-mediated protein deglycation.Structure (London, England : 1993) · 2024Article
- TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression.Nature communications · 2024Article
- Breaking tolerance: autoantibodies can target protein posttranslational modifications.Current opinion in biotechnology · 2024Review
- Immunotherapy targeting isoDGR-protein damage extends lifespan in a mouse model of protein deamidation.EMBO molecular medicine · 2023Article
- Red Blood Cells from Individuals with Lesch-Nyhan Syndrome: Multi-Omics Insights into a Novel S162N Mutation Causing Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency.Antioxidants (Basel, Switzerland) · 2023Article
- Red Blood Cell Metabolism In Vivo and In Vitro.Metabolites · 2023Review
- Bioinformatics of cyanophycin metabolism genes and characterization of promiscuous isoaspartyl dipeptidases that catalyze the final step of cyanophycin degradation.Scientific reports · 2023Article
- Article
- Characterization of a polyclonal antibody that is highly selective for the D-isoAsp-25 variant of mammalian histone H2B.Amino acids · 2023Article
- Discovery of cyanophycin dipeptide hydrolase enzymes suggests widespread utility of the natural biopolymer cyanophycin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Biological effects of the loss of homochirality in a multicellular organism.Nature communications · 2022Article
- Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
L-Asparaginyl and L-aspartyl residues in proteins are subject to spontaneous degradation reactions that generate isomerized and racemized aspartyl derivatives. Proteins containing L-isoaspartyl and D-aspartyl residues can have altered structures and diminished biological activity. These residues are recognized by a highly conserved cytosolic enzyme, the protein L-isoaspartate(D-aspartate) O-methyltransferase (EC 2.1.1.77). The enzymatic methyl esterification of these abnormal residues in vitro can lead to their conversion (i.e., repair) to normal L-aspartyl residues and should therefore prevent the accumulation of potentially dysfunctional proteins in vivo as cells and tissues age. Particularly high levels of the repair methyltransferase are present in the brain, although enyzme activity is present in all vertebrate tissues. To define the physiological relevance of this protein-repair pathway and to determine whether deficient protein repair would cause central nervous system dysfunction, we used gene targeting in mouse embryonic stem cells to generate protein L-isoaspartate(D-aspartate) O-methyltransferase-deficient mice. Analyses of tissues from methyltransferase knockout mice revealed a striking accumulation of protein substrates for this enzyme in the cytosolic fraction of brain, heart, liver, and erythrocytes. The knockout mice showed significant growth retardation and succumbed to fatal seizures at an average of 42 days after birth. These results suggest that the ability of mice to repair L-isoaspartyl- and D-aspartyl-containing proteins is essential for normal growth and for normal central nervous system function.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.