Identification of Pyruvate Dehydrogenase E1 as a Potential Target against Magnaporthe oryzae through Experimental and Theoretical Investigation

Abstract

Magnaporthe oryzae (M. oryzae) is a typical cause of rice blast in agricultural production. Isobavachalcone (IBC), an active ingredient of Psoralea corylifolia L. extract, is an effective fungicide against rice blast. To determine the mechanism of IBC against M. oryzae, the effect of IBC on the metabolic pathway of M. oryzae was explored by transcriptome profiling. In M. oryzae, the expression of pyruvate dehydrogenase E1 (PDHE1), part of the tricarboxylic acid (TCA cycle), was significantly decreased in response to treatment with IBC, which was verified by qPCR and testing of enzyme activity. To further elucidate the interactions between IBC and PDHE1, the 3D structure model of the PDHE1 from M. oryzae was established based on homology modeling. The model was utilized to analyze the molecular interactions through molecular docking and molecular dynamics simulation, revealing that IBC has π-π stacking interactions with residue TYR139 and undergoes hydrogen bonding with residue ASP217 of PDHE1. Additionally, the nonpolar residues PHE111, MET174, ILE 187, VAL188, and MET250 form strong hydrophobic interactions with IBC. The above results reveal that PDHE1 is a potential target for antifungal agents, which will be of great significance for guiding the design of new fungicides. This research clarified the mechanism of IBC against M. oryzae at the molecular level, which will underpin further studies of the inhibitory mechanism of flavonoids and the discovery of new targets. It also provides theoretical guidance for the field application of IBC.

Novel Galactosyl Moiety-Conjugated Furylchalcones Synthesized Facilely Display Significant Regulatory Effect on Plant Growth

“…16 Moreover, the fungistatic and fungicidal effects of chalcones have also been investigated against phytopathogens in greater detail, including geranyl chalcones, 17 chalcone-based strobilurins, 18 dihydrochalcones (mainly phloridzin, sieboldin, trilobatin, and phloretin), 19 vanillin-chalcones, 20 ferrocenyl-chalcones, 21 isobavachalcones, 22 dihydrochromane-chalcones, 23 and isobavachalcones. 24 In contrast, the herbicidal activity of chalcones has been less investigated. Only some chalcone derivatives as inhibitors of phosphoenolpyruvate carboxylase, photosystem II, or plant growth and the herbicidal activity of flavokawains have been identified; 25−27 thus, the richly natural chalcones as herbicides are waiting to be further developed and utilized for crop protection.…”

“…These compounds or chalcone-rich plant extracts have competed for substantial research attention as drugs or food preservatives for decades. , Chalcones exhibit numerous interesting biological activities such as anti-cancer, anti-inflammatory, anti-hypertensive, anti-oxidant, anti-viral, anti-bacterial, and anti-microbial activities, which were several times reviewed. − Recently, it has been reported that chalcones have been served as novel insecticides to control insect population, such as angular benzofuran chalcones, chemically modified chalcones, the chalcone derivatives kanakugiol, hydroxychalcone and cardamonin, and furan-chalcones . Moreover, the fungistatic and fungicidal effects of chalcones have also been investigated against phytopathogens in greater detail, including geranyl chalcones, chalcone-based strobilurins, dihydrochalcones (mainly phloridzin, sieboldin, trilobatin, and phloretin), vanillin-chalcones, ferrocenyl-chalcones, isobavachalcones, dihydrochromane-chalcones, and isobavachalcones . In contrast, the herbicidal activity of chalcones has been less investigated.…”

Active site-specific quantum tunneling of hACE2 receptor to assess its complexing poses with selective bioactive compounds in co-suppressing SARS-CoV-2 influx and subsequent cardiac injury

“…In this research, Desmond (Desmond, Schrödinger, LLC, NY) has been used for molecular dynamic simulation (MDS) that was operated to investigate the receptor RMSD, receptor RMSF, Intra H-bonds, Cα, SASA, MolSA, Rg, and PSA for 20 ns. The RMSD values are considered to measure the average shift in a set of atoms for a specific frame with a reference frame [ 51 ]. This parameter governs a significant role in assisting the comparisons among different molecular structures and narrows down the extensive list of predictive conformations to a smaller set [ 52 ].…”

Isobavachalcone: A comprehensive review of its plant sources, pharmacokinetics, toxicity, pharmacological activities and related molecular mechanisms

“…IBC also has certain antibacterial activity against Mycobacterium tuberculosis (Chiang et al, 2010; Pollo et al, 2020). IBC can bind to PDHE1 of magnaporthe grisea to inhibit carbohydrate metabolism and eventually lead to the gradual destruction and death of mycelium cells (Li et al, 2021). In addition, IBC has certain anti‐trichomonas activity (Omisore et al, 2005).…”