%0 Journal Article
%T Structural identification and comprehension of human ALDH1L1-Gossypol complex.
%A Han CW
%A Lee HN
%A Jeong MS
%A Kim HY
%A Jang SB
%J Biochem Biophys Res Commun
%V 726
%N 0
%D 2024 Sep 24
%M 38917634
%F 3.322
%R 10.1016/j.bbrc.2024.150306
%X The folate metabolism enzyme ALDH1L1 catalyzed 10-formyltetrahydrofolate to tetrahydrofolate and CO2. 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.