8Y2N

Cryo-EM structure of the apo Lac1-Lip1 complex

8Y2N の概要

• エントリーDOI: 10.2210/pdb8y2n/pdb
• EMDBエントリー: 38857 38858
• 分子名称: Ceramide synthase LAC1, Ceramide synthase subunit LIP1, (4S,7R)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSAN-1-AMINIUM 4-OXIDE (3 entities in total)
• 機能のキーワード: inhibitor, complex, transferase
• 由来する生物種: Saccharomyces cerevisiae S288C (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 141140.33

構造登録者

Xie, T.,Zhang, Z.,Fang, Q.,Gong, X. (登録日: 2024-01-26, 公開日: 2024-11-27)

主引用文献

Zhang, Z.,Fang, Q.,Xie, T.,Gong, X.
Mechanism of ceramide synthase inhibition by fumonisin B 1.
Structure, 32:1419-1428.e4, 2024

PubMed Abstract: Ceramide synthases (CerSs) play crucial roles in sphingolipid metabolism and have emerged as promising drug targets for metabolic diseases, cancers, and antifungal therapy. However, the therapeutic targeting of CerSs has been hindered by a limited understanding of their inhibition mechanisms by small molecules. Fumonisin B (FB) has been extensively studied as a potent inhibitor of eukaryotic CerSs. In this study, we characterize the inhibition mechanism of FB on yeast CerS (yCerS) and determine the structures of both FB-bound and N-acyl-FB-bound yCerS. Through our structural analysis and the observation of N-acylation of FB by yCerS, we propose a potential ping-pong catalytic mechanism for FB N-acylation by yCerS. Lastly, we demonstrate that FB exhibits lower binding affinity for yCerS compared to the C26- coenzyme A (CoA) substrate, suggesting that the potent inhibitory effect of FB on yCerS may primarily result from the N-acyl-FB catalyzed by yCerS, rather than through direct binding of FB.

PubMed: 38964337
DOI: 10.1016/j.str.2024.06.002

実験手法

ELECTRON MICROSCOPY (3.19 Å)