8DAE

Arabidopsis thaliana bifunctional dihydrofolate reductase-thymidylate synthase

8DAE の概要

• エントリーDOI: 10.2210/pdb8dae/pdb
• 分子名称: Bifunctional dihydrofolate reductase-thymidylate synthase 1 (2 entities in total)
• 機能のキーワード: apo, transferase, oxidoreductase
• 由来する生物種: Arabidopsis thaliana (thale cress)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 60276.37

構造登録者

Bond, C.S.,Haywood, J. (登録日: 2022-06-13, 公開日: 2023-06-21, 最終更新日: 2026-02-04)

主引用文献

Haywood, J.,Breese, K.J.,McDougal, D.P.,Verdonk, C.,Partridge, A.,Lo, A.F.,Zhang, J.,Yang, W.C.,Bruning, J.B.,Saliba, K.J.,Bond, C.S.,Stubbs, K.A.,Mylne, J.S.
Structural insights into a plant-conserved DHFR-TS reveal a selective herbicide target.
Mol Plant, 18:1294-1309, 2025

PubMed Abstract: Modern agricultural practices rely on herbicides to reduce yield losses. Herbicide-resistant weeds threaten herbicide utility and, hence, food security. New herbicide modes of action and integrated pest-management practices are vital to mitigate this threat. As the antimalarials that target the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) have been shown to be herbicidal, DHFR-TS might represent a mode-of-action target for the development of herbicides. Here, we present the crystal structure of a DHFR-TS (AtDHFR-TS1) from the model dicot Arabidopsis thaliana. It shows a divergent DHFR active site and a linker domain that challenges previous classifications of bifunctional DHFR-TS proteins. This plant-conserved architecture enabled us to develop highly selective herbicidal inhibitors of AtDHFR-TS1 over human DHFR and identify inhibitors with unique scaffolds via a large-library virtual screen. These results suggest that DHFR-TS is a viable herbicide target.

PubMed: 40598768
DOI: 10.1016/j.molp.2025.06.016

実験手法

X-RAY DIFFRACTION (2 Å)