7MPY
Crystal structure of cytosolic HPPK-DHPS from A.thaliana
Summary for 7MPY
| Entry DOI | 10.2210/pdb7mpy/pdb |
| Descriptor | Folate synthesis bifunctional protein (2 entities in total) |
| Functional Keywords | folate biosynthesis, herbicide target, plant protein, transferase |
| Biological source | Arabidopsis thaliana (thale cress) |
| Total number of polymer chains | 2 |
| Total formula weight | 112506.98 |
| Authors | Vadlamani, G.,Bond, C.S. (deposition date: 2021-05-05, release date: 2021-12-08, Last modification date: 2023-10-18) |
| Primary citation | 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 Cited by 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: 35605193DOI: 10.1016/j.xplc.2022.100322 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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