Crystal structure of Arabidopsis thaliana HPPK/DHPS, a bifunctional enzyme and target of the herbicide asulam

通讯单位：澳大利亚西澳大学

背景介绍：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 while still in widespread use, asulam has faced regulatory scrutiny. 

除草剂对现代农业很重要，但是农药的有效性受到杂草遗传、代谢抗性和调控阻碍的威胁。在已知的除草剂作用模式中，参与草酸生物合成的DHPS只是一种商业除草剂阿舒蓝靶标。由于整个作用方式代表的只是一种商业的除草剂，因此应该提升它对植物靶标的认识。由于只有一种商业农用化学品代表了整个行动模式，我们试图提高对其植物目标的理解。

研究内容：With an entire mode of action represented by just one commercial agrochemical, we sought to improve the understanding of its plant target. 

该研究解决了与6-羟甲基-7，8-HPPK连接的拟南芥DHPS的2.3Å分辨率晶体结构，并揭示了在DHPS的磺胺结合口袋处与细菌同行的强烈结构保守。

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 reveal a strong structural conservation with bacterial counterparts at the sulfonamide-binding pocket of DHPS. We demonstrate asulam and the antibiotic sulfamethoxazole have herbicidal as well as antibacterial activity and explore the structural basis of their potency by modelling these compounds in mitochondrial HPPK/DHPS. Our findings suggest limited opportunity for the rational design of plant selectivity from asulam and that pharmacokinetic or delivery differences between plants and microbes might be the best ways to safeguard this mode of action.

该研究解决了拟南芥结合HPPK到DHPS的结构，揭示一个保守结构。该研究通过在线粒体的HPPK/DHPS模拟这些化合物，阐明了 asulam 和antibiotic sulfamethoxazole有除草和抗菌活力，并探索到它们效力的结构基础。我们的发现合理设计植物的选择性的机会有限，植物和微生物之间的药代动力学或给药差异可能是保护这一作用模式的最佳方式。

原文链接：https://www.sciencedirect.com/science/article/pii/S2590346222000724?via%3Dihub

Journal: Plant Communications

First Published:  April 9, 2022