ArticleThe Journal of biological chemistry2014
A glutathione-independent glyoxalase of the DJ-1 superfamily plays an important role in managing metabolically generated methylglyoxal in Candida albicans.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 89 citations in OpenAlex.
- Current potential biomarkers for Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis: review of literature.Dialogues in clinical neuroscience · 2026Review
- Mapping the Molecular Evolution and Role of Wild Rice GLYIII Protein-Encoding Genes in Abiotic Stress Response.Biochemical genetics · 2026Article
- Towards time-resolved MicroED grid preparation using mix-and-inject gas dynamic virtual nozzles.IUCrJ · 2026Article
- Glyoxalase activities of Parkinson's disease relevant protein DJ-1/PARK7: Past discoveries and future perspectives.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2026Review
- Leveraging Vulnerabilities in Copper Trafficking for Synergistic Antifungal Activity.ACS chemical biology · 2025Article
- Effects of low intracellular glutathione and CbrA-CbrB-Crc signaling on methylglyoxal sensitivity inJournal of bacteriology · 2025Article
- Does Gut Microbial Methylglyoxal Metabolism Impact Human Physiology?Antioxidants (Basel, Switzerland) · 2025Review
- Tracing the intraspecies expansion of glyoxalase genes and their expanding roles across the genus Oryza.Functional & integrative genomics · 2024Article
- The origin of esterase activity of Parkinson's disease causative factor DJ-1 implied by evolutionary trace analysis of its prokaryotic homolog HchA.The Journal of biological chemistry · 2024Article
- Physiological adventures inMicrobiology and molecular biology reviews : MMBR · 2024Review
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- Disruption of lysosomal proteolysis in astrocytes facilitates midbrain organoid proteostasis failure in an early-onset Parkinson's disease model.Nature communications · 2024Article
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- Photosynthesis regulation, cell membrane stabilization and methylglyoxal detoxification seems major altered pathways under cold stress as revealed by integrated multi-omics meta-analysis.Physiology and molecular biology of plants : an international journal of functional plant biology · 2023Article
- DJ-1 is not a deglycase and makes a modest contribution to cellular defense against methylglyoxal damage in neurons.Journal of neurochemistry · 2022Article
- RNA-Seq Based Transcriptome Analysis ofJournal of fungi (Basel, Switzerland) · 2022Article
- GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products.BMC biology · 2022Article
- Exploration of the regulatory mechanisms of regeneration, anti-oxidation, anti-aging and the immune response at the post-molt stage ofFrontiers in physiology · 2022Article
- Global transcriptome profiling reveals genes responding to overproduction of a small secretory, a high cysteine- and a high glycosylation-bearing protein inBiotechnology reports (Amsterdam, Netherlands) · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Methylglyoxal is a cytotoxic reactive carbonyl compound produced by central metabolism. Dedicated glyoxalases convert methylglyoxal to d-lactate using multiple catalytic strategies. In this study, the DJ-1 superfamily member ORF 19.251/GLX3 from Candida albicans is shown to possess glyoxalase activity, making this the first demonstrated glutathione-independent glyoxalase in fungi. The crystal structure of Glx3p indicates that the protein is a monomer containing the catalytic triad Cys(136)-His(137)-Glu(168). Purified Glx3p has an in vitro methylglyoxalase activity (Km = 5.5 mM and kcat = 7.8 s(-1)) that is significantly greater than that of more distantly related members of the DJ-1 superfamily. A close Glx3p homolog from Saccharomyces cerevisiae (YDR533C/Hsp31) also has glyoxalase activity, suggesting that fungal members of the Hsp31 clade of the DJ-1 superfamily are all probable glutathione-independent glyoxalases. A homozygous glx3 null mutant in C. albicans strain SC5314 displays greater sensitivity to millimolar levels of exogenous methylglyoxal, elevated levels of intracellular methylglyoxal, and carbon source-dependent growth defects, especially when grown on glycerol. These phenotypic defects are complemented by restoration of the wild-type GLX3 locus. The growth defect of Glx3-deficient cells in glycerol is also partially complemented by added inorganic phosphate, which is not observed for wild-type or glucose-grown cells. Therefore, C. albicans Glx3 and its fungal homologs are physiologically relevant glutathione-independent glyoxalases that are not redundant with the previously characterized glutathione-dependent GLO1/GLO2 system. In addition to its role in detoxifying glyoxals, Glx3 and its close homologs may have other important roles in stress response.
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