3THR

Crystal structure of rat native liver Glycine N-methyltransferase complexed with 5-methyltetrahydrofolate monoglutamate

3THR の概要

• エントリーDOI: 10.2210/pdb3thr/pdb
• 関連するPDBエントリー: 2IDK 3THS
• 分子名称: Glycine N-methyltransferase, 5-METHYL-5,6,7,8-TETRAHYDROFOLIC ACID, TRIS(HYDROXYETHYL)AMINOMETHANE, ... (4 entities in total)
• 機能のキーワード: glycine n-methyltransferase, gnmt, folate, methyltransferase, folate binding, liver cytosol, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• 細胞内の位置: Cytoplasm: P13255
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 132274.95

構造登録者

Luka, Z.,Pakhomova, S.,Loukachevitch, L.V.,Newcomer, M.E.,Wagner, C. (登録日: 2011-08-19, 公開日: 2011-11-16, 最終更新日: 2024-11-06)

主引用文献

Luka, Z.,Pakhomova, S.,Loukachevitch, L.V.,Newcomer, M.E.,Wagner, C.
Differences in folate-protein interactions result in differing inhibition of native rat liver and recombinant glycine N-methyltransferase by 5-methyltetrahydrofolate.
Biochim.Biophys.Acta, 1824:286-291, 2011

PubMed Abstract: Glycine N-methyltransferase (GNMT) is a key regulatory enzyme in methyl group metabolism. In mammalian liver it reduces S-adenosylmethionine levels by using it to methylate glycine, producing N-methylglycine (sarcosine) and S-adenosylhomocysteine. GNMT is inhibited by binding two molecules of 5-methyltetrahydrofolate (mono- or polyglutamate forms) per tetramer of the active enzyme. Inhibition is sensitive to the status of the N-terminal valine of GNMT and to polyglutamation of the folate inhibitor. It is inhibited by pentaglutamate form more efficiently compared to monoglutamate form. The native rat liver GNMT contains an acetylated N-terminal valine and is inhibited much more efficiently compared to the recombinant protein expressed in E. coli where the N-terminus is not acetylated. In this work we used a protein crystallography approach to evaluate the structural basis for these differences. We show that in the folate-GNMT complexes with the native enzyme, two folate molecules establish three and four hydrogen bonds with the protein. In the folate-recombinant GNMT complex only one hydrogen bond is established. This difference results in more effective inhibition by folate of the native liver GNMT activity compared to the recombinant enzyme.

PubMed: 22037183
DOI: 10.1016/j.bbapap.2011.10.008

実験手法

X-RAY DIFFRACTION (2 Å)