5A19

The structure of MAT2A in complex with PPNP.

Summary for 5A19

• Entry DOI: 10.2210/pdb5a19/pdb
• Related: 5A1G 5A1I
• Descriptor: S-ADENOSYLMETHIONINE SYNTHASE ISOFORM TYPE-2, DI(HYDROXYETHYL)ETHER, (DIPHOSPHONO)AMINOPHOSPHONIC ACID, ... (8 entities in total)
• Functional Keywords: transferase, methionine adenosyltransferase, cell growth, liver cancer, methylation.
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 44721.77

Authors

Murray, B.,Antonyuk, S.V.,Marina, A.,Lu, S.C.,Mato, J.M.,Hasnain, S.S.,Rojas, A.L. (deposition date: 2015-04-28, release date: 2016-02-17, Last modification date: 2024-01-10)

Primary citation

Murray, B.,Antonyuk, S.V.,Marina, A.,Lu, S.C.,Mato, J.M.,Hasnain, S.S.,Rojas, A.L.
Crystallography Captures Catalytic Steps in Human Methionine Adenosyltransferase Enzymes.
Proc.Natl.Acad.Sci.USA, 113:2104-, 2016

PubMed 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.

PubMed: 26858410
DOI: 10.1073/PNAS.1510959113

Experimental method

X-RAY DIFFRACTION (2.34 Å)