ArticleBiomolecules2019
Structural and Functional Analyses of Human ChaC2 in Glutathione Metabolism.
Article in Biomolecules, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- CHAC2-mediated glutathione metabolic reprogramming drives N1 polarization of bone marrow neutrophils and exacerbates inflammatory comorbidities.International journal of oral science · 2026Article
- Article
- The strategic breakdown: CHAC enzymes as regulators of glutathione homeostasis and disease implications.Frontiers in molecular biosciences · 2025Review
- CHAC1 in urological tumors: contextual dualism and therapeutic implications.Frontiers in oncology · 2025Review
- Nanopore sequencing as a novel method of characterising anorexia nervosa risk loci.BMC genomics · 2024Article
- Glutathione‑degrading enzymes in the complex landscape of tumors (Review).International journal of oncology · 2024Review
- Mitochondrial respiratory function is preserved under cysteine starvation via glutathione catabolism in NSCLC.Nature communications · 2024Article
- An mRNA vaccine for pancreatic cancer designed by applying in silico immunoinformatics and reverse vaccinology approaches.PloS one · 2024Article
- Adh PromotesCells · 2023Article
- CHAC2 promotes lung adenocarcinoma by regulating ROS-mediated MAPK pathway activation.Journal of Cancer · 2023Article
- Transcript profiling of glutathione metabolizing genes reveals abiotic stress and glutathione-specific alteration inPhysiology and molecular biology of plants : an international journal of functional plant biology · 2022Article
- Cysteine metabolic circuitries: druggable targets in cancer.British journal of cancer · 2021Review
- Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glutathione (GSH) degradation plays an essential role in GSH homeostasis, which regulates cell survival, especially in cancer cells. Among human GSH degradation enzymes, the ChaC2 enzyme acts on GSH to form 5-l-oxoproline and Cys-Gly specifically in the cytosol. Here, we report the crystal structures of ChaC2 in two different conformations and compare the structural features with other known γ-glutamylcyclotransferase enzymes. The unique flexible loop of ChaC2 seems to function as a gate to achieve specificity for GSH binding and regulate the constant GSH degradation rate. Structural and biochemical analyses of ChaC2 revealed that Glu74 and Glu83 play crucial roles in directing the conformation of the enzyme and in modulating the enzyme activity. Based on a docking study of GSH to ChaC2 and binding assays, we propose a substrate-binding mode and catalytic mechanism. We also found that overexpression of ChaC2, but not mutants that inhibit activity of ChaC2, significantly promoted breast cancer cell proliferation, suggesting that the GSH degradation by ChaC2 affects the growth of breast cancer cells. Our structural and functional analyses of ChaC2 will contribute to the development of inhibitors for the ChaC family, which could effectively regulate the progression of GSH degradation-related cancers.
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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.