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

Plant Communications 2022年第4期3卷 137-149页

作者： Grishma Vadlamani Kirill V.Sukhoverkov Joel Haywood Karen J.Breese Mark F.Fisher keith a.stubbs Charles S.Bond Joshua S.Mylne School of Molecular Sciences The University of Western Australia35 Stirling HighwayCrawleyWA 6009Australia The ARC Centre of Excellence in Plant Energy Biology The University of Western Australia35 Stirling HighwayCrawleyWA 6009Australia Centre for Crop and Disease Management School of Molecular and Life SciencesCurtin UniversityBentleyWA 6102Australia

Herbicides are vital formodern agriculture,but their utility is threatened by genetic or metabolic resistance in weeds,as well as regulatory *** 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 *** an entire mode of action represented by just one commercial agrochemical,we sought to improve the understanding of its plant *** we solve a 2.3A°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-bindingpocket of *** demonstrate that asulamand the antibiotic sulfamethoxazole have herbicidal as well as antibacterial activity,andwe explore the structural basis of their potency by modeling these compounds in mitochondrial HPPK/*** findings suggest limited opportunity for the rational design of plant selectivity fromasulamand indicate that pharmacokinetic or delivery differences between plants andmicrobesmight be the bestways to safeguard thismode of action.

关键词： structural biology folate metabolism mode of action

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