Comparative structural and functional analysis of phi class glutathione transferases involved in multiple-herbicide resistance of grass weeds and crops

Georgakis, Nikolaos; Poudel, Nirmal; Papageorgiou, Anastassios C.; Labrou, Nikolaos E.

doi:10.1016/j.plaphy.2020.02.012

Cited by 15 publications

(28 citation statements)

References 61 publications

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“…The closed loop conformation was observed in the recent independent crystal structure determination of AmGSTF1 in a different crystal form. 17 As described in more detail below, a similar closed conformation was subsequently confirmed in the AmGSTF1 variant structures and with native AmGSTF1 bound to S-glutathionylated-NBD in a third crystal form. The cores of all of these structures superimpose very well, with an rmsd of approximately 0.4 Å (Fig.…”

Section: Crystal Structure Of Wild-type Amgstf1supporting

confidence: 57%

Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance

et al. 2021

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Section: Crystal Structure Of Wild-type Amgstf1supporting

confidence: 57%

Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance

et al. 2021

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“…Enzymes (LrGSTF, NCBI accession number: CCO25537.1; AmGSTF, NCBI accession number: CAA09192.1; HvGSTF, NCBI accession number: AAL73394.1; TaGSTF, NCBI accession number: AAL47688.1) were cloned, expressed in E. coli and purified by affinity chromatography as described by Georgakis et al (2020).…”

Section: Enzyme Expression and Purificationmentioning

confidence: 99%

“…The mixture was incubated at 25 • C for 1 min, before adding CDNB. The concentration of CDNB was adjusted to equal the K m(CDNB) value (Georgakis et al, 2020) of the examined enzyme (1.0 mM for AmGSTF, 0.73 mM for LrGSTF, 1.0 mM for HvGSTF and 0.78 mM for TaGSTF). The observed reaction rates were used to calculate the remaining activity (%) taking as 100% the initial enzyme activity determined in the absence of inhibitor.…”

Section: Screening Of Pesticide Natural Product and S-alkyl-gsh-inhimentioning

confidence: 99%

“…Plant GSTs have been identified as major mediators of metabolic resistance to herbicides through their catalytic activity to conjugate the tripeptide glutathione (GSH) to a wide range of herbicides (Busi et al, 2018;Gaines et al, 2020;Gao et al, 2019;Nakka et al, 2017). A specific phi class glutathione transferase (MHR-GSTF) that also exhibits high glutathione peroxidase activity has been identified as a major factor (Cummins et al, 1999(Cummins et al, , 2013Georgakis et al, 2020;Pégeot et al, 2017) that confers resistance against multiple herbicides through multiple mechanisms (Tétard-Jones et al, 2018). Because of the rapid spread of MHR in weeds and the restricted development of new herbicides, the identification of synergistic compounds which when combined with the existing herbicides can inhibit MHR-GSTF and therefore restore weed control in MHR weeds would certainly be an important development.…”

Section: Introductionmentioning

confidence: 99%

“…Each subunit has an independent active site that is formed by two distinct sub-sites: the GSH-binding site (G-site) in the N-terminal domain and an electrophile substrate-binding site (H-site) in the C-terminal domain as in other GST classes (Axarli et al, 2009a(Axarli et al, , 2009bNeuefeind et al, 1997). The N-terminal domain is conserved among different isoenzymes, whereas the C-terminal domain is quite variable, thus leading to distinct specificities toward the xenobiotic substrate (Axarli et al, 2009a(Axarli et al, , 2009bDixon et al, 2010;Dixon and Edwards, 2009;Georgakis et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Phi class glutathione transferases as molecular targets towards multiple-herbicide resistance: Inhibition analysis and pharmacophore design

Georgakis

Poudel

Vlachakis

et al. 2021

Plant Physiology and Biochemistry

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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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Metagenomic analysis of hot spring soil for mining a novel thermostable enzybiotic

Pantiora,

Georgakis,

Premetis

et al. 2024

Appl Microbiol Biotechnol

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The misuse and overuse of antibiotics have contributed to a rapid emergence of antibiotic-resistant bacterial pathogens. This global health threat underlines the urgent need for innovative and novel antimicrobials. Endolysins derived from bacteriophages or prophages constitute promising new antimicrobials (so-called enzybiotics), exhibiting the ability to break down bacterial peptidoglycan (PG). In the present work, metagenomic analysis of soil samples, collected from thermal springs, allowed the identification of a prophage-derived endolysin that belongs to the N-acetylmuramoyl-L-alanine amidase type 2 (NALAA-2) family and possesses a LysM (lysin motif) region as a cell wall binding domain (CWBD). The enzyme (Ami1) was cloned and expressed in Escherichia coli, and its bactericidal and lytic activity was characterized. The results indicate that Ami1 exhibits strong bactericidal and antimicrobial activity against a broad range of bacterial pathogens, as well as against isolated peptidoglycan (PG). Among the examined bacterial pathogens, Ami1 showed highest bactericidal activity against Staphylococcus aureus sand Staphylococcus epidermidis cells. Thermostability analysis revealed a melting temperature of 64.2 ± 0.6 °C. Overall, these findings support the potential that Ami1, as a broad spectrum antimicrobial agent, could be further assessed as enzybiotic for the effective treatment of bacterial infections. Key points • Metagenomic analysis allowed the identification of a novel prophage endolysin • The endolysin belongs to type 2 amidase family with lysin motif region • The endolysin displays high thermostability and broad bactericidal spectrum

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Comparative structural and functional analysis of phi class glutathione transferases involved in multiple-herbicide resistance of grass weeds and crops

Cited by 15 publications

References 61 publications

Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance

Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance

Phi class glutathione transferases as molecular targets towards multiple-herbicide resistance: Inhibition analysis and pharmacophore design

Metagenomic analysis of hot spring soil for mining a novel thermostable enzybiotic

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