2AZT

Crystal structure of H176N mutant of human Glycine N-Methyltransferase

2AZT の概要

• エントリーDOI: 10.2210/pdb2azt/pdb
• 関連するPDBエントリー: 1R74
• 分子名称: Glycine N-methyltransferase, BETA-MERCAPTOETHANOL, CITRIC ACID, ... (5 entities in total)
• 機能のキーワード: glycine n-methyltransferase, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q14749
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66330.79

構造登録者

Luka, Z.,Pakhomova, S.,Luka, Y.,Newcomer, M.E.,Wagner, C. (登録日: 2005-09-12, 公開日: 2006-09-26, 最終更新日: 2023-08-23)

主引用文献

Luka, Z.,Pakhomova, S.,Luka, Y.,Newcomer, M.E.,Wagner, C.
Destabilization of human glycine N-methyltransferase by H176N mutation.
Protein Sci., 16:1957-1964, 2007

PubMed Abstract: In the presence of moderate (2-4 M) urea concentrations the tetrameric enzyme, glycine N-methyltransferase (GNMT), dissociates into compact monomers. Higher concentrations of urea (7-8 M) promote complete denaturation of the enzyme. We report here that the H176N mutation in this enzyme, found in humans with hypermethioninaemia, significantly decreases stability of the tetramer, although H176 is located far from the intersubunit contact areas. Dissociation of the tetramer to compact monomers and unfolding of compact monomers of the mutant protein were detected by circular dichroism, quenching of fluorescence emission, size-exclusion chromatography, and enzyme activity. The values of apparent free energy of dissociation of tetramer and of unfolding of compact monomers for the H176N mutant (27.7 and 4.2 kcal/mol, respectively) are lower than those of wild-type protein (37.5 and 6.2 kcal/mol). A 2.7 A resolution structure of the mutant protein revealed no significant difference in the conformation of the protein near the mutated residue.

PubMed: 17660255
DOI: 10.1110/ps.072921507

実験手法

X-RAY DIFFRACTION (2.7 Å)