+検索条件
-Structure paper
タイトル | Structural identification and comprehension of human ALDH1L1-Gossypol complex. |
---|---|
ジャーナル・号・ページ | Biochem Biophys Res Commun, Vol. 726, Page 150306, Year 2024 |
掲載日 | 2024年9月24日 |
著者 | Chang Woo Han / Han Na Lee / Mi Suk Jeong / Hong Yeoul Kim / Se Bok Jang / |
PubMed 要旨 | The folate metabolism enzyme ALDH1L1 catalyzed 10-formyltetrahydrofolate to tetrahydrofolate and CO. Non-small cell lung cancer cells (NSCLC) strongly express ALDH1L1. Gossypol binds to an allosteric ...The folate metabolism enzyme ALDH1L1 catalyzed 10-formyltetrahydrofolate to tetrahydrofolate and CO. Non-small cell lung cancer cells (NSCLC) strongly express ALDH1L1. Gossypol binds to an allosteric site and disrupts the folate metabolism by preventing NADP binding. The Cryo-EM structures of tetrameric C-terminal aldehyde dehydrogenase human ALDH1L1 complex with gossypol were examined. Gossypol-bound ALDH1L1 interfered with NADP by shifting the allosteric site of the structural conformation, producing a closed-form NADP binding site. In addition, the inhibition activity of ALDH1L1 was targeted with gossypol in NSCLC. The gossypol treatment had anti-cancer effects on NSCLC by blocking NADPH and ATP production. These findings emphasize the structure characterizing ALDH1L1 with gossypol. |
リンク | Biochem Biophys Res Commun / PubMed:38917634 |
手法 | EM (単粒子) |
解像度 | 6.31 Å |
構造データ | EMDB-33872, PDB-7yjj: |
化合物 | ChemComp-GO3: |
由来 |
|
キーワード | OXIDOREDUCTASE / Cytosolic 10-formyltetrahydrofolate dehydrogenase / Aldehyde dehydrogenase family 1 member L1 / inhibitor / Gossypol |