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Phi class glutathione transferases as molecular targets towards multiple-herbicide resistance: Inhibition analysis and pharmacophore design
Tekijät: Georgakis N, Poudel N, Vlachakis D, Papageorgiou AC, Labrou NE
Kustantaja: Elsevier Masson
Julkaisuvuosi: 2021
Journal: Plant Physiology and Biochemistry
Tietokannassa oleva lehden nimi: Plant physiology and biochemistry : PPB
Lehden akronyymi: Plant Physiol Biochem
Vuosikerta: 158
Sivujen määrä: 11
ISSN: 0981-9428
eISSN: 1873-2690
DOI: https://doi.org/10.1016/j.plaphy.2020.11.018
Tiivistelmä
Multiple-herbicide resistance (MHR) is a global threat to weed control in cereal crops. MHR weeds express a specific phi class glutathione transferase (MHR-GSTF) that confers resistance against multiple herbicides and therefore represents a promising target against MHR weeds. Kinetics inhibition analysis of MHR-GSTFs from grass weeds Lolium rigidum (LrGSTF) Alopecurus myosuroides (AmGSTF) and crops Hordeum vulgare (HvGSTF) and Triticum aestivum (TaGSTF) allowed the identification of the acetanilide herbicide butachlor as a potent and selective inhibitor towards MHR-GSTFs. Also, butachlor is a stronger inhibitor for LrGSTF and AmGSTF compared to HvGSTF and TaGSTF from crops. The crystal structure of LrGSTF was determined at 1.90 Å resolution in complex with the inhibitor S-(4-nitrobenzyl)glutathione. A specific 3D pharmacophore targeting the MHR-GSTFs was designed and used to identify structural elements important for potent and selective inhibition. Structural analysis of GSTFs revealed a decisive role of conserved Tyr118 in ligand binding and pharmacophore design. Its positioning is dependent on an outer patch of adjacent residues that span from position 132 to 134 which are similar for both LrGSTF and AmGSTF but different in HvGSTF and TaGSTF. The results presented here provide new knowledge that may be adopted to cope with MHR weeds.
Multiple-herbicide resistance (MHR) is a global threat to weed control in cereal crops. MHR weeds express a specific phi class glutathione transferase (MHR-GSTF) that confers resistance against multiple herbicides and therefore represents a promising target against MHR weeds. Kinetics inhibition analysis of MHR-GSTFs from grass weeds Lolium rigidum (LrGSTF) Alopecurus myosuroides (AmGSTF) and crops Hordeum vulgare (HvGSTF) and Triticum aestivum (TaGSTF) allowed the identification of the acetanilide herbicide butachlor as a potent and selective inhibitor towards MHR-GSTFs. Also, butachlor is a stronger inhibitor for LrGSTF and AmGSTF compared to HvGSTF and TaGSTF from crops. The crystal structure of LrGSTF was determined at 1.90 Å resolution in complex with the inhibitor S-(4-nitrobenzyl)glutathione. A specific 3D pharmacophore targeting the MHR-GSTFs was designed and used to identify structural elements important for potent and selective inhibition. Structural analysis of GSTFs revealed a decisive role of conserved Tyr118 in ligand binding and pharmacophore design. Its positioning is dependent on an outer patch of adjacent residues that span from position 132 to 134 which are similar for both LrGSTF and AmGSTF but different in HvGSTF and TaGSTF. The results presented here provide new knowledge that may be adopted to cope with MHR weeds.
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