ArticleNature chemical biology2017
Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 131 citations in OpenAlex.
- Integrating proteomics and metabolomics to reveal MAT2A for metabolic reprogramming in non-small cell lung cancer cells.iScience · 2026Article
- Acetoacetate-GPR43 axis epigenetically silences IL-6/CSF1 to restrict TAMs-driven metastatic lung cancer.Journal of translational medicine · 2026Article
- Targeting methionine-induced pyroptosis enhances anti-tumor immunity.Science China. Life sciences · 2026Article
- MTAP-Null Tumors: A Comprehensive Review on Synthetic Vulnerabilities and Therapeutic Strategies.Cells · 2025Review
- Targeting MAT2A synergistically induces DNA damage in osteosarcoma cells through EZH2-mediated H3K27me3 modification.Journal of orthopaedic translation · 2025Article
- IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation.Cell reports · 2025Article
- A genome-scale drug discovery pipeline uncovers therapeutic targets and a unique p97 allosteric binding site inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The catalytic efficiency of METTL16 affects cellular processes by governing the intracellular S-adenosylmethionine setpoint.Cell reports · 2025Article
- Glioma promotes macrophage immunosuppressive phenotype through ANXA1 in a methionine metabolism-dependent manner.Discover oncology · 2025Article
- Lipoic acid functions in Paneth cells to prevent human intestinal stem cell aging.Nature communications · 2025Article
- Discovery of Potential Scaffolds for Methionine Adenosyltransferase 2A (MAT2A) Inhibitors: Virtual Screening, Synthesis, and Biological Evaluation.Molecules (Basel, Switzerland) · 2025Article
- Methionine Dependency and Restriction in Cancer: Exploring the Pathogenic Function and Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Structure-Based Discovery of a Series of Novel MAT2a Inhibitors.ACS medicinal chemistry letters · 2025Article
- Methionine intervention induces PD-L1 expression to enhance the immune checkpoint therapy response in MTAP-deleted osteosarcoma.Cell reports. Medicine · 2025Article
- A genome-scale drug discovery pipeline uncovers new therapeutic targets and a unique p97 allosteric binding site inbioRxiv : the preprint server for biology · 2025Article
- Methionine-SAM metabolism-dependent ubiquinone synthesis is crucial for ROS accumulation in ferroptosis induction.Nature communications · 2024Article
- SCR-7952, a highly selective MAT2A inhibitor, demonstrates synergistic antitumor activities in combination with theMedComm · 2024Article
- MAT2B regulates the protein level of MAT2A to preserve RNA N6-methyladenosine.Cell death & disease · 2024Article
- Inhibition of MAT2A Impairs Skeletal Muscle Repair Function.Biomolecules · 2024Article
- Epigenome-wide impact of MAT2A sustains the androgen-indifferent state and confers synthetic vulnerability in ERG fusion-positive prostate cancer.Nature communications · 2024Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
S-Adenosyl-L-methionine (SAM) is an enzyme cofactor used in methyl transfer reactions and polyamine biosynthesis. The biosynthesis of SAM from ATP and L-methionine is performed by the methionine adenosyltransferase enzyme family (Mat; EC 2.5.1.6). Human methionine adenosyltransferase 2A (Mat2A), the extrahepatic isoform, is often deregulated in cancer. We identified a Mat2A inhibitor, PF-9366, that binds an allosteric site on Mat2A that overlaps with the binding site for the Mat2A regulator, Mat2B. Studies exploiting PF-9366 suggested a general mode of Mat2A allosteric regulation. Allosteric binding of PF-9366 or Mat2B altered the Mat2A active site, resulting in increased substrate affinity and decreased enzyme turnover. These data support a model whereby Mat2B functions as an inhibitor of Mat2A activity when methionine or SAM levels are high, yet functions as an activator of Mat2A when methionine or SAM levels are low. The ramification of Mat2A activity modulation in cancer cells is also described.
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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.