ArticleProceedings of the National Academy of Sciences of the United States of America2016
Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- Prevalence of heterozygous and homozygous 9p21 deletions in human cancer: a tissue microarray study on 4,999 tumors from 125 different tumor types.Molecular medicine (Cambridge, Mass.) · 2026Article
- MTAP deficiency is highly homogeneous in advanced, muscle-invasive urothelial carcinoma of the urinary bladder.Scientific reports · 2025Article
- Combined inhibition by PRMT5 and MAT2A demonstrates a strong synthetic lethality in MTAP homozygous-deficient glioma models.Cell death discovery · 2025Article
- Deficiency of MTAP Is Frequent and Mostly Homogeneous in Pancreatic Ductal Adenocarcinomas.Cancers · 2025Article
- Posttranslational Regulation of Mammalian Sulfur Amino Acid Metabolism.International journal of molecular sciences · 2025Review
- Loss of MTAP expression is strongly linked to homozygous 9p21 deletion, unfavorable tumor phenotype, and noninflamed microenvironment in urothelial bladder cancer.The journal of pathology. Clinical research · 2025Article
- MAT2B regulates the protein level of MAT2A to preserve RNA N6-methyladenosine.Cell death & disease · 2024Article
- Double-duty isomerases: a case study of isomerization-coupled enzymatic catalysis.Trends in biochemical sciences · 2024Review
- Development of Novel Nano-Sized Imine Complexes UsingInternational journal of molecular sciences · 2023Article
- Synthesis of a new sulfadimidine Schiff base and their nano complexes as potential anti-COVID-19 and anti-cancer activity.Scientific reports · 2023Article
- The potential and challenges of targetingFrontiers in oncology · 2023Review
- One Carbon Metabolism andLivers · 2022Article
- mTORC1-c-Myc pathway rewires methionine metabolism for HCC progression through suppressing SIRT4 mediated ADP ribosylation of MAT2A.Cell & bioscience · 2022Article
- Substrate Dynamics Contribute to Enzymatic Specificity in Human and Bacterial Methionine Adenosyltransferases.JACS Au · 2021Article
- Polar Interactions at the Dimer-Dimer Interface of Methionine Adenosyltransferase MAT I Control Tetramerization.International journal of molecular sciences · 2021Article
- Human Mat2A Uses an Ordered Kinetic Mechanism and Is Stabilized but Not Regulated by Mat2B.Biochemistry · 2021Article
- Mechanism of Triphosphate Hydrolysis by Human MAT2A at 1.07 Å Resolution.Journal of the American Chemical Society · 2021Article
- GABA transporter sustains IL-1β production in macrophages.Science advances · 2021Article
- Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A.Biochemistry · 2021Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
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Abstract
The principal methyl donor of the cell, S-adenosylmethionine (SAMe), is produced by the highly conserved family of methionine adenosyltranferases (MATs) via an ATP-driven process. These enzymes play an important role in the preservation of life, and their dysregulation has been tightly linked to liver and colon cancers. We present crystal structures of human MATα2 containing various bound ligands, providing a "structural movie" of the catalytic steps. High- to atomic-resolution structures reveal the structural elements of the enzyme involved in utilization of the substrates methionine and adenosine and in formation of the product SAMe. MAT enzymes are also able to produce S-adenosylethionine (SAE) from substrate ethionine. Ethionine, an S-ethyl analog of the amino acid methionine, is known to induce steatosis and pancreatitis. We show that SAE occupies the active site in a manner similar to SAMe, confirming that ethionine also uses the same catalytic site to form the product SAE.
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