3FVS

Human Kynurenine Aminotransferase I in complex with Glycerol

3FVS の概要

• エントリーDOI: 10.2210/pdb3fvs/pdb
• 関連するPDBエントリー: 3FVU
• 分子名称: Kynurenine--oxoglutarate transaminase 1, SODIUM ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: alpha beta protein, plp dependent protein, aminotransferase, lyase, pyridoxal phosphate, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q16773
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96450.07

構造登録者

Han, Q.,Robinson, H.,Cai, T.,Tagle, D.A.,Li, J. (登録日: 2009-01-16, 公開日: 2009-05-19, 最終更新日: 2023-11-22)

主引用文献

Han, Q.,Robinson, H.,Cai, T.,Tagle, D.A.,Li, J.
Structural insight into the inhibition of human kynurenine aminotransferase I/glutamine transaminase K
J.Med.Chem., 52:2786-2793, 2009

PubMed Abstract: Human kynurenine aminotransferase I (hKAT I) catalyzes the formation of kynurenic acid, a neuroactive compound. Here, we report three high-resolution crystal structures (1.50-1.55 A) of hKAT I that are in complex with glycerol and each of two inhibitors of hKAT I: indole-3-acetic acid (IAC) and Tris. Because Tris is able to occupy the substrate binding position, we speculate that this may be the basis for hKAT I inhibition. Furthermore, the hKAT/IAC complex structure reveals that the binding moieties of the inhibitor are its indole ring and a carboxyl group. Six chemicals with both binding moieties were tested for their ability to inhibit hKAT I activity; 3-indolepropionic acid and DL-indole-3-lactic acid demonstrated the highest level of inhibition, and as they cannot be considered as substrates of the enzyme, these two inhibitors are promising candidates for future study. Perhaps even more significantly, we report the discovery of two different ligands located simultaneously in the hKAT I active center for the first time.

PubMed: 19338303
DOI: 10.1021/jm9000874

実験手法

X-RAY DIFFRACTION (1.5 Å)