3PAA

Mechanism of inactivation of E. coli aspartate aminotransferase by (S)-4-amino-4,5-dihydro-2-furancarboxylic acid (S-ADFA) pH 8.0

3PAA の概要

• エントリーDOI: 10.2210/pdb3paa/pdb
• 関連するPDBエントリー: 3PA9
• 分子名称: Aspartate aminotransferase, 4-aminofuran-2-carboxylic acid, 4'-DEOXY-4'-AMINOPYRIDOXAL-5'-PHOSPHATE, ... (6 entities in total)
• 機能のキーワード: pmp, sadfa, transferase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45391.77

構造登録者

Liu, D.,Pozharski, E.,Fu, M.,Silverman, R.B.,Ringe, D. (登録日: 2010-10-19, 公開日: 2010-12-01, 最終更新日: 2024-10-30)

主引用文献

Liu, D.,Pozharski, E.,Fu, M.,Silverman, R.B.,Ringe, D.
Mechanism of inactivation of Escherichia coli aspartate aminotransferase by (S)-4-amino-4,5-dihydro-2-furancarboxylic acid .
Biochemistry, 49:10507-10515, 2010

PubMed Abstract: As a potential drug to treat neurological diseases, the mechanism-based inhibitor (S)-4-amino-4,5-dihydro-2-furancarboxylic acid (S-ADFA) has been found to inhibit the γ-aminobutyric acid aminotransferase (GABA-AT) reaction. To circumvent the difficulties in structural studies of a S-ADFA-enzyme complex using GABA-AT, l-aspartate aminotransferase (l-AspAT) from Escherichia coli was used as a model PLP-dependent enzyme. Crystal structures of the E. coli aspartate aminotransferase with S-ADFA bound to the active site were obtained via cocrystallization at pH 7.5 and 8. The complex structures suggest that S-ADFA inhibits the transamination reaction by forming adducts with the catalytic lysine 246 via a covalent bond while producing 1 equiv of pyridoxamine 5'-phosphate (PMP). Based on the structures, formation of the K246-S-ADFA adducts requires a specific initial binding configuration of S-ADFA in the l-AspAT active site, as well as deprotonation of the ε-amino group of lysine 246 after the formation of the quinonoid and/or ketimine intermediate in the overall inactivation reaction.

PubMed: 21033689
DOI: 10.1021/bi101325z

実験手法

X-RAY DIFFRACTION (1.9 Å)