7MPY

Crystal structure of cytosolic HPPK-DHPS from A.thaliana

7MPY の概要

• エントリーDOI: 10.2210/pdb7mpy/pdb
• 分子名称: Folate synthesis bifunctional protein (2 entities in total)
• 機能のキーワード: folate biosynthesis, herbicide target, plant protein, transferase
• 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: 112506.98

構造登録者

Vadlamani, G.,Bond, C.S. (登録日: 2021-05-05, 公開日: 2021-12-08, 最終更新日: 2023-10-18)

主引用文献

Vadlamani, G.,Sukhoverkov, K.V.,Haywood, J.,Breese, K.J.,Fisher, M.F.,Stubbs, K.A.,Bond, C.S.,Mylne, J.S.
Crystal structure of Arabidopsis thaliana HPPK/DHPS, a bifunctional enzyme and target of the herbicide asulam.
Plant Commun., 3:100322-100322, 2022

PubMed Abstract: Herbicides are vital for modern agriculture, but their utility is threatened by genetic or metabolic resistance in weeds, as well as regulatory barriers. Of the known herbicide modes of action, 7,8-dihydropterin synthase (DHPS), which is involved in folate biosynthesis, is targeted by just one commercial herbicide, asulam. A mimic of the substrate para-aminobenzoic acid, asulam is chemically similar to sulfonamide antibiotics, and although it is still in widespread use, asulam has faced regulatory scrutiny. With an entire mode of action represented by just one commercial agrochemical, we sought to improve the understanding of its plant target. Here we solve a 2.3 Å resolution crystal structure for Arabidopsis thaliana DHPS that is conjoined to 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), and we reveal a strong structural conservation with bacterial counterparts at the sulfonamide-binding pocket of DHPS. We demonstrate that asulam and the antibiotic sulfamethoxazole have herbicidal as well as antibacterial activity, and we explore the structural basis of their potency by modeling these compounds in mitochondrial HPPK/DHPS. Our findings suggest limited opportunity for the rational design of plant selectivity from asulam and indicate that pharmacokinetic or delivery differences between plants and microbes might be the best ways to safeguard this mode of action.

PubMed: 35605193
DOI: 10.1016/j.xplc.2022.100322

実験手法

X-RAY DIFFRACTION (2.3 Å)