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.
journal_name
Proc Natl Acad Sci U S Aauthors
Murray B,Antonyuk SV,Marina A,Lu SC,Mato JM,Hasnain SS,Rojas ALdoi
10.1073/pnas.1510959113subject
Has Abstractpub_date
2016-02-23 00:00:00pages
2104-9issue
8eissn
0027-8424issn
1091-6490pii
1510959113journal_volume
113pub_type
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