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

Grishma Vadlamani, Kirill V Sukhoverkov, Joel Haywood, Karen J Breese, Mark F Fisher, Keith A Stubbs, Charles S Bond, Joshua S Mylne

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number100322
JournalPlant Communications
Issue number4
Early online date9 Apr 2022
Publication statusPublished - 11 Jul 2022


Dive into the research topics of 'Crystal structure of Arabidopsis thaliana HPPK/DHPS, a bifunctional enzyme and target of the herbicide asulam'. Together they form a unique fingerprint.

Cite this