2IDK

Crystal Structure of Rat Glycine N-Methyltransferase Complexed With Folate

2IDK の概要

• エントリーDOI: 10.2210/pdb2idk/pdb
• 関連するPDBエントリー: 1BHJ 1NBH 1NBI 1R74 1R8X 2IDJ
• 分子名称: Glycine N-methyltransferase, 5-METHYL-5,6,7,8-TETRAHYDROFOLIC ACID (3 entities in total)
• 機能のキーワード: glycine n-methyltransferase, rat, folate binding, transferase
• 由来する生物種: Rattus norvegicus (Norway rat)
• 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: 130762.23

構造登録者

Luka, Z.,Pakhomova, S.,Loukachevitch, L.V.,Egli, M.,Newcomer, M.E.,Wagner, C. (登録日: 2006-09-15, 公開日: 2006-12-19, 最終更新日: 2023-08-30)

主引用文献

Luka, Z.,Pakhomova, S.,Loukachevitch, L.V.,Egli, M.,Newcomer, M.E.,Wagner, C.
5-methyltetrahydrofolate is bound in intersubunit areas of rat liver folate-binding protein glycine N-methyltransferase.
J.Biol.Chem., 282:4069-4075, 2007

PubMed Abstract: Glycine N-methyltransferase (GNMT) is a key regulatory enzyme in methyl group metabolism. It is abundant in the liver, where it uses excess S-adenosylmethionine (AdoMet) to methylate glycine to N-methylglycine (sarcosine) and produces S-adenosylhomocysteine (AdoHcy), thereby controlling the methylating potential of the cell. GNMT also links utilization of preformed methyl groups, in the form of methionine, to their de novo synthesis, because it is inhibited by a specific form of folate, 5-methyltetrahydrofolate. Although the structure of the enzyme has been elucidated by x-ray crystallography of the apoenzyme and in the presence of the substrate, the location of the folate inhibitor in the tetrameric structure has not been identified. We report here for the first time the crystal structure of rat GNMT complexed with 5-methyltetrahydrofolate. In the GNMT-folate complex, two folate binding sites were located in the intersubunit areas of the tetramer. Each folate binding site is formed primarily by two 1-7 N-terminal regions of one pair of subunits and two 205-218 regions of the other pair of subunits. Both the pteridine and p-aminobenzoyl rings are located in the hydrophobic cavities formed by Tyr5, Leu207, and Met215 residues of all subunits. Binding experiments in solution also confirm that one GNMT tetramer binds two folate molecules. For the enzymatic reaction to take place, the N-terminal fragments of GNMT must have a significant degree of conformational freedom to provide access to the active sites. The presence of the folate in this position provides a mechanism for its inhibition.

PubMed: 17158459
DOI: 10.1074/jbc.M610384200

実験手法

X-RAY DIFFRACTION (2.55 Å)