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Antimalarial drug resistance has thrown a spanner in the works of malaria elimination. New drugs are required for ancillary support of existing malaria control efforts. Plasmodium falciparum requires host glucose for survival and proliferation. On this basis, P . falciparum hexose transporter 1 ( Pf HT1) protein involved in hexose permeation is considered a potential drug target. In this study, we tested the antimalarial activity of some compounds against Pf HT1 using computational techniques. We performed high throughput virtual screening of 21,352 small-molecule compounds against Pf HT1. The stability of the lead compound complexes was evaluated via molecular dynamics (MD) simulation for 100 nanoseconds. We also investigated the pharmacodynamic, pharmacokinetic and physiological characteristics of the compounds in accordance with Lipinksi rules for drug-likeness to bind and inhibit Pf HT1. Molecular docking and free binding energy analyses were carried out using Molecular Mechanics with Generalized Born and Surface Area (MMGBSA) solvation to determine the selectivity of the hit compounds for Pf HT1 over the human glucose transporter (hGLUT1) orthologue. Five important Pf HT1 inhibitors were identified: Hyperoside (CID5281643); avicularin (CID5490064); sylibin (CID5213); harpagoside (CID5481542) and quercetagetin (CID5281680). The compounds formed intermolecular interaction with the binding pocket of the Pf HT1 target via conserved amino acid residues (Val314, Gly183, Thr49, Asn52, Gly183, Ser315, Ser317, and Asn48). The MMGBSA analysis of the complexes yielded high free binding energies. Four (CID5281643, CID5490064, CID5213, and CID5481542) of the identified compounds were found to be stable within the Pf HT1 binding pocket throughout the 100 nanoseconds simulation run time. The four compounds demonstrated higher affinity for Pf HT1 than the human major glucose transporter (hGLUT1). This investigation demonstrates the inhibition potential of sylibin, hyperoside, harpagoside, and avicularin against Pf HT1 receptor. Robust preclinical investigations are required to validate the chemotherapeutic properties of the identified compounds.

Key message OsSWEET1b is a hexose transporter protein , which localized in cell membranes and interacting with itself to form homodimer and knockout of OsSWEET1b resulted in reduced leaves sugar content and accelerating leaf senescence. In the rice genome, the SWEET gene family contains 21 homologous members, but the role of some of them in rice growth and development is still unknown. The function of the sugar transporter OsSWEET1b protein in rice was identified in this research. Expression analysis showed that the expression levels of OsSWEET1b in leaves were higher than that in other tissues. The hexose transport experiment confirmed that OsSWEET1b has glucose and galactose transporter activity in yeast. Subcellular localization indicates that OsSWEET1b protein was targeted to the plasma membrane and BiFC analysis showed that OsSWEET1b interacts with itself to form homodimers. Functional analysis demonstrated that the ossweet1b mutant plants were have reduced the sucrose, glucose, fructose, starch and galactose contents, and induced carbon starvation-related gene expression, which might lead to carbon starvation in leaves at filling stage. The ossweet1b knockout plants showed decreased chlorophyll content and antioxidant enzyme activity, and increased ROS accumulation in leaves, leading to leaf cell death and premature senescence phenotype at filling stage. In ossweet1b mutants, the leaf senescence-related gene expression levels were increased and the abundance of photosynthesis-related proteins was decreased. Loss of OsSWEET1b were affected the starch, sucrose metabolism and carbon fixation in photosynthetic organelles pathway by RNA-seq analysis. The destruction of OsSWEET1b function will cause sugar starvation, decreased photosynthesis and leaf senescence, which leading to reduced rice yield. Collectively, our results suggest that the OsSWEET1b plays a key role in rice leaves carbohydrate metabolism and leaf senescence.

Antimalarial drug resistance has thrown a spanner in the works of malaria elimination. New drugs are required for ancillary support of existing malaria control efforts. Plasmodium falciparum requires host glucose for survival and proliferation. On this basis, P . falciparum hexose transporter 1 ( Pf HT1) protein involved in hexose permeation is considered a potential drug target. In this study, we tested the antimalarial activity of some compounds against Pf HT1 using computational techniques. We performed high throughput virtual screening of 21,352 small-molecule compounds against Pf HT1. The stability of the lead compound complexes was evaluated via molecular dynamics (MD) simulation for 100 nanoseconds. We also investigated the pharmacodynamic, pharmacokinetic and physiological characteristics of the compounds in accordance with Lipinksi rules for drug-likeness to bind and inhibit Pf HT1. Molecular docking and free binding energy analyses were carried out using Molecular Mechanics with Generalized Born and Surface Area (MMGBSA) solvation to determine the selectivity of the hit compounds for Pf HT1 over the human glucose transporter (hGLUT1) orthologue. Five important Pf HT1 inhibitors were identified: Hyperoside (CID5281643); avicularin (CID5490064); sylibin (CID5213); harpagoside (CID5481542) and quercetagetin (CID5281680). The compounds formed intermolecular interaction with the binding pocket of the Pf HT1 target via conserved amino acid residues (Val314, Gly183, Thr49, Asn52, Gly183, Ser315, Ser317, and Asn48). The MMGBSA analysis of the complexes yielded high free binding energies. Four (CID5281643, CID5490064, CID5213, and CID5481542) of the identified compounds were found to be stable within the Pf HT1 binding pocket throughout the 100 nanoseconds simulation run time. The four compounds demonstrated higher affinity for Pf HT1 than the human major glucose transporter (hGLUT1). This investigation demonstrates the inhibition potential of sylibin, hyperoside, harpagoside, and avicularin against Pf HT1 receptor. Robust preclinical investigations are required to validate the chemotherapeutic properties of the identified compounds.

Artemisinin-resistant malaria parasites have emerged and have been spreading, posing a significant public health challenge. Antimalarial drugs with novel mechanisms of action are therefore urgently needed. In this report, we exploit a “selective starvation” strategy by inhibiting Plasmodium falciparum hexose transporter 1 (PfHT1), the sole hexose transporter in P. falciparum, over human glucose transporter 1 (hGLUT1), providing an alternative approach to fight against multidrug-resistant malaria parasites. The crystal structure of hGLUT3, which shares 80% sequence similarity with hGLUT1, was resolved in complex with C3361, a moderate PfHT1-specific inhibitor, at 2.3-Å resolution. Structural comparison between the present hGLUT3-C3361 and our previously reported PfHT1-C3361 confirmed the unique inhibitor binding-induced pocket in PfHT1. We then designed small molecules to simultaneously block the orthosteric and allosteric pockets of PfHT1. Through extensive structure–activity relationship studies, the TH-PF series was identified to selectively inhibit PfHT1 over hGLUT1 and potent against multiple strains of the blood-stage P. falciparum. Our findings shed light on the next-generation chemotherapeutics with a paradigm-shifting structure-based design strategy to simultaneously target the orthosteric and allosteric sites of a transporter.

Necrosis and ethylene-inducing peptide 1–like (NLP) proteins constitute a superfamily of proteins produced by plant pathogenic bacteria, fungi, and oomycetes. Many NLPs are cytotoxins that facilitate microbial infection of eudicot, but not of monocot plants. Here, we report glycosylinositol phosphorylceramide (GIPC) sphingolipids as NLP toxin receptors. Plant mutants with altered GIPC composition were more resistant to NLP toxins. Binding studies and x-ray crystallography showed that NLPs form complexes with terminal monomeric hexose moieties of GIPCs that result in conformational changes within the toxin. Insensitivity to NLP cytolysins of monocot plants may be explained by the length of the GIPC head group and the architecture of the NLP sugar-binding site. We unveil early steps in NLP cytolysin action that determine plant clade-specific toxin selectivity.

The basic requirements for plant growth are light, CO2, water, and minerals. However, the absorption and utilization of each of these requires investment on the part of the plant. The primary products of plants are sugars, and the hexose sugars glucose and fructose are the raw material for most of the metabolic pathways and organic matter in plants. To be metabolized, hexose sugars must first be phosphorylated. Only two families of enzymes capable of catalysing the essential irreversible phosphorylation of glucose and fructose have been identified in plants, hexokinases (HXKs) and fructokinases (FRKs). These hexose-phosphorylating enzymes appear to coordinate sugar production with the abilities to absorb light, CO2, water, and minerals. This review describes the long- and short-term effects mediated by HXK and FRK in various tissues, as well as the role of these enzymes in the coordination of sugar production with the absorption of light, CO2, water, and minerals.

Reaumuria soongorica is an important biological barrier for ecological protection in the Gobi Desert in northwestern China, where soil nitrogen availability is low. N deposition has recently increased significantly in Gobi Desert, and the responses of R. soongorica to N enrichment may become a problem for ecological restoration and protection. However, little is known about the effects of N addition on the biomass, non-structural carbohydrates (NSC), and carbon:nitrogen:phosphorus (C:N:P) stoichiometry of R. soongorica in this region. Here, we examined changes in biomass, NSC and C:N:P ratios of different organs of R. soongorica seedlings in four N addition treatments: 0 (N 0 ), 4.6 (N 1 ), 9.2 (N 2 ), and 13.8 (N 3 ) g m −2  year −1 . N addition up to 9.2 g m −2  year −1 significantly increased the biomass of different organs, simultaneously increasing the belowground: aboveground ratio of R. soongorica seedlings. Root NSC concentrations significantly increased under all N addition treatments, but leaf and stem NSC concentrations only increased under the N 1 and N 2 addition treatments. Nitrogen addition enhanced the soluble sugar concentrations (SSC) of leaves and roots, and reduced starch concentrations (SC) of all organs. Stem and root N concentrations significantly increased under the N 2 and N 3 treatments, and leaf N concentrations only increased under the N 3 treatment, but N addition had no significant effect on plant C and P concentrations. Leaf and stem C:N ratios decreased significantly under the N 2 and N 3 treatments, but root C:N decreased significantly in all N addition treatments. The N 3 treatment significantly increased the N:P ratio of all organs. N addition significantly enhanced available N (AN), available P (AP) and total phosphorus (TP) in rhizosphere soil. Our results suggest that N addition alters the biomass, NSC, N concentrations, C:N and N:P ratios of all plant organs, but roots responded more strongly than stems or leaves to N addition, potentially allowing the plants to absorb more water from the arid soil in this region ensuring the survival of R. soongorica seedlings. Rhizosphere soil AP, AN and TP concentrations were important factors affecting the NSC concentrations and stoichiometric characteristics of R. soongorica .

The first analytical method is presented for the identification and absolute configuration determination of all 24 aldohexose and 2-ketohexose isomers, including the D and L enantiomers for allose, altrose, galactose, glucose, gulose, idose, mannose, talose, fructose, psicose, sorbose, and tagatose. Two unique fixed ligand kinetic method combinations were discovered to create significant enough energetic differences to achieve chiral discrimination among all 24 hexoses. Each of these 24 hexoses yields unique ratios of a specific pair of fragment ions that allows for simultaneous determination of identification and absolute configuration. This mass spectrometric-based methodology can be readily employed for accurate identification of any isolated monosaccharide from an unknown biological source. This work provides a key step towards the goal of complete de novo carbohydrate analysis. Graphical Abstract ᅟ

Summary Although great progress has been made towards understanding the role of abscisic acid (ABA) and sucrose in fruit ripening, the mechanisms underlying the ABA and sucrose signalling pathways remain elusive. In this study, transcription factor ABA‐stress‐ripening (ASR), which is involved in the transduction of ABA and sucrose signalling pathways, was isolated and analysed in the nonclimacteric fruit, strawberry and the climacteric fruit, tomato. We have identified four ASR isoforms in tomato and one in strawberry. All ASR sequences contained the ABA stress‐ and ripening‐induced proteins and water‐deficit stress‐induced proteins (ABA/WDS) domain and all ASR transcripts showed increased expression during fruit development. The expression of the ASR gene was influenced not only by sucrose and ABA, but also by jasmonic acid (JA) and indole‐3‐acetic acid (IAA), and these four factors were correlated with each other during fruit development. ASR bound the hexose transporter (HT) promoter, which contained a sugar box that activated downstream gene expression. Overexpression of the ASR gene promoted fruit softening and ripening, whereas RNA interference delayed fruit ripening, as well as affected fruit physiological changes. Change in ASR gene expression influenced the expression of several ripening‐related genes such as CHS, CHI, F3H, DFR, ANS, UFGT, PG, PL, EXP1/2, XET16, Cel1/2 and PME. Taken together, this study may provide new evidence on the important role of ASR in cross‐signalling between ABA and sucrose to regulate tomato and strawberry fruit ripening. The findings of this study also provide new insights into the regulatory mechanism underlying fruit development.

Abstract Iron is an essential cofactor for eukaryotic cells, as well as a toxic metal under certain conditions. On the other hand, glucose is the preferred energy and carbon source by most organisms and is an important signaling molecule in the regulation of biological processes. In Schizosaccharomyces pombe, the Ght5 hexose transporter, known as a high affinity glucose transporter, is required for cell proliferation in low glucose concentrations. Herein, we aimed to investigate the effects of iron stress on the Ght5 hexose transporter under glucose repression and derepression conditions. The effect of iron stress on the expression profile of the ght5 gene was analyzed by RT-qPCR and western blot. The localization of the Ght5-mNeonGreen fusion protein examined with confocal microscopy. Our results revealed that iron stress had an inhibitory effect on ght5 expression, and it altered Ght5 localization on the cell surface, causing it to accumulate in the cytoplasm. Effects of iron stress on Ght5, hexose transporter of Schizosaccaromyces pombe, under glucose repression and de-repression conditions were investigated.