8IMU

Dihydroxyacid dehydratase (DHAD) mutant-V497F

8IMU の概要

• エントリーDOI: 10.2210/pdb8imu/pdb
• 分子名称: Dihydroxy-acid dehydratase, chloroplastic, FE2/S2 (INORGANIC) CLUSTER, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: [2fe-2s] cluster, aspterric acid, bcaa biosynthetic pathway, lyase
• 由来する生物種: Arabidopsis thaliana (thale cress)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123027.62

構造登録者

Zhou, J.,Zang, X.,Tang, Y.,Yan, Y. (登録日: 2023-03-07, 公開日: 2024-03-13, 最終更新日: 2024-11-20)

主引用文献

Zang, X.,Bat-Erdene, U.,Huang, W.,Wu, Z.,Jacobsen, S.E.,Tang, Y.,Zhou, J.
Structural Bases of Dihydroxy Acid Dehydratase Inhibition and Biodesign for Self-Resistance.
Biodes Res, 6:0046-0046, 2024

PubMed Abstract: Dihydroxy acid dehydratase (DHAD) is the third enzyme in the plant branched-chain amino acid biosynthetic pathway and the target for commercial herbicide development. We have previously reported the discovery of fungal natural product aspterric acid (AA) as a submicromolar inhibitor of DHAD through self-resistance gene directed genome mining. Here, we reveal the mechanism of AA inhibition on DHAD and the self-resistance mechanism of AstD, which is encoded by the self-resistance gene D. As a competitive inhibitor, the hydroxycarboxylic acid group of AA mimics the binding of the natural substrate of DHAD, while the hydrophobic moiety of AA occupies the substrate entrance cavity. Compared to DHAD, AstD has a relatively narrow substrate channel to prevent AA from binding. Several mutants of DHAD were generated and assayed to validate the self-resistance mechanism and to confer DHAD with AA resistance. These results will lead to the engineering of new type of herbicides targeting DHAD and provide direction for the ecological construction of herbicide-resistant crops.

PubMed: 39494391
DOI: 10.34133/bdr.0046

実験手法

X-RAY DIFFRACTION (1.93 Å)