Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes Academic Article uri icon


MeSH Major

  • Methionine Adenosyltransferase
  • S-Adenosylmethionine


  • 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 MATĪ±2 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.

publication date

  • February 23, 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC4776477

Digital Object Identifier (DOI)

  • 10.1073/pnas.1510959113

PubMed ID

  • 26858410

Additional Document Info

start page

  • 2104

end page

  • 9


  • 113


  • 8