8IMU

Dihydroxyacid dehydratase (DHAD) mutant-V497F

Summary for 8IMU

• Entry DOI: 10.2210/pdb8imu/pdb
• Descriptor: Dihydroxy-acid dehydratase, chloroplastic, FE2/S2 (INORGANIC) CLUSTER, ACETATE ION, ... (5 entities in total)
• Functional Keywords: [2fe-2s] cluster, aspterric acid, bcaa biosynthetic pathway, lyase
• Biological source: Arabidopsis thaliana (thale cress)
• Total number of polymer chains: 2
• Total formula weight: 123027.62

Authors

Zhou, J.,Zang, X.,Tang, Y.,Yan, Y. (deposition date: 2023-03-07, release date: 2024-03-13, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.93 Å)