Novel coumarin-6-sulfonamide-chalcone hybrids as glutathione transferase P1-1 inhibitors.

Multidrug resistance (MDR) mechanisms in cancer cells are greatly influenced by glutathione transferase P1-1 (hGSTP1-1). The use of synthetic or natural compounds as hGSTP1-1 inhibitors is considered an effective approach to overcome MDR. Nine compounds consisting of coumarin-6-sulfonamide linked to chalcone derivatives were synthesized and evaluated for their ability to inhibit hGSTP1-1.

A Monocarbonyl Curcuminoid Derivative Inhibits the Activity of Human Glutathione Transferase A4-4 and Chemosensitizes Glioblastoma Cells to Temozolomide.

Human glutathione transferase A4-4 (hGSTA4-4) displays high catalytic efficiency towards 4-hydroxyalkenals and other cytotoxic and mutagenic products of radical reactions and lipid peroxidation. Its role as a target for the chemosensitization of cancer cells has not been investigated so far. In this study, the inhibitory potency of twelve selected natural products and ten monocarbonyl curcumin derivatives against hGSTA4-4 was studied.

Structural Studies of Fosfomycin-Resistance Protein and Its Application for the Development of an Optical Biosensor for Fosfomycin Determination.

Fosfomycin-resistance proteins (FosAs) are dimeric metal-dependent glutathione transferases that conjugate the antibiotic fosfomycin (Fos) to the tripeptide glutathione (γ-Glu-Cys-Gly, GSH), rendering it inactive. In the present study, we reported a comparative analysis of the functional features of two FosAs from (FosAPA) and (FosAKP). The coding sequences of the enzymes were cloned into a T7 expression vector, and soluble active enzymes were expressed in .

Inhibition Analysis and High-Resolution Crystal Structure of Glutathione Transferase P1-1.

Multidrug resistance is a significant barrier that makes anticancer therapies less effective. Glutathione transferases (GSTs) are involved in multidrug resistance mechanisms and play a significant part in the metabolism of alkylating anticancer drugs. The purpose of this study was to screen and select a lead compound with high inhibitory potency against the isoenzyme GSTP1-1 from (GSTP1-1).

Structural and functional features of a broad-spectrum prophage-encoded enzybiotic from Enterococcus faecium.

Multidrug-resistant (MDR) bacteria have become a growing threat to public health. The gram-positive Enterococcus faecium is classified by WHO as a high-priority pathogen among the global priority list of antibiotic-resistant bacteria. Peptidoglycan-degrading enzymes (PDEs), also known as enzybiotics, are useful bactericidal agents in the fight against resistant bacteria.

A Key Role in Catalysis and Enzyme Thermostability of a Conserved Helix H5 Motif of Human Glutathione Transferase A1-1.

Glutathione transferases (GSTs) are promiscuous enzymes whose main function is the detoxification of electrophilic compounds. These enzymes are characterized by structural modularity that underpins their exploitation as dynamic scaffolds for engineering enzyme variants, with customized catalytic and structural properties. In the present work, multiple sequence alignment of the alpha class GSTs allowed the identification of three conserved residues (E137, K141, and S142) at α-helix 5 (H5).

Monocarbonyl Curcumin Analogues as Potent Inhibitors against Human Glutathione Transferase P1-1.

The isoenzyme of human glutathione transferase P1-1 (hGSTP1-1) is involved in multi-drug resistance (MDR) mechanisms in numerous cancer cell lines. In the present study, the inhibition potency of two curcuminoids and eleven monocarbonyl curcumin analogues against hGSTP1-1 was investigated. Demethoxycurcumin (Curcumin II) and three of the monocarbonyl curcumin analogues exhibited the highest inhibitory activity towards hGSTP1-1 with IC values ranging between 5.

Characterization of a glycoside hydrolase endolysin from Acinetobacter baumannii phage AbTZA1 with high antibacterial potency and novel structural features.

The classification of Acinetobacter baumannii by WHO as 'priority 1' antibiotic-resistant pathogen underlines the urgent need for novel antimicrobial agents towards this pathogen. In this work, screening of the A. baumannii phage AbTZA1 genome allowed the identification of a putative endolysin (AbLys1, EC3.

Small-Molecule-based Supramolecular Plastics Mediated by Liquid-Liquid Phase Separation.

Plastics are one of the most widely used polymeric materials. However, they are often undegradable and non-recyclable due to the very stable covalent bonds of macromolecules, causing environmental pollution and health problems. Here, we report that liquid-liquid phase separation (LLPS) could drive the formation of robust, stable, and sustainable plastics using small molecules.

Directed Evolution of Phi Class Glutathione Transferases Involved in Multiple-Herbicide Resistance of Grass Weeds and Crops.

The extensive application of herbicides in crop cultivation has indisputably led to the emergence of weed populations characterized by multiple herbicide resistance (MHR). This phenomenon is associated with the enhanced metabolism and detoxifying ability of endogenous enzymes, such as phi class glutathione transferases (GSTFs). In the present work, a library of mutant GSTFs was created by in vitro directed evolution via DNA shuffling.

Structural Characterization of Multienzyme Assemblies: An Overview.

Multienzyme assemblies have attracted significant attention in recent years for use in industrial applications instead of single enzymes. Owing to their ability to catalyze cascade reactions, multienzyme assemblies have become inspirational tools for the in vitro construction of multienzyme molecular machines. The use of such molecular machines could offer several advantages such as fewer side reactions, a high product yield, a fast reaction speed, easy product separation, a tolerable toxic environment, and robust system operability compared to current microbial cell catalytic systems.

Ligandability Assessment of Human Glutathione Transferase M1-1 Using Pesticides as Chemical Probes.

Glutathione transferases (GSTs; EC 2.5.1.

Structural and Functional Characterization of Glutathione Transferase M1-1.

Glutathione transferases (GSTs; EC. 2.5.

Crystal Structure of a Cu,Zn Superoxide Dismutase From the Thermophilic Fungus Chaetomium thermophilum.

Background: Thermophilic fungi have recently emerged as a promising source of thermostable enzymes. Superoxide dismutases are key antioxidant metalloenzymes with promising therapeutic effects in various diseases, both acute and chronic. However, structural heterogeneity and low thermostability limit their therapeutic efficacy.

Mesoporous Carbon Microfibers for Electroactive Materials Derived from Lignocellulose Nanofibrils.

The growing adoption of biobased materials for electronic, energy conversion, and storage devices has relied on high-grade or refined cellulosic compositions. Herein, lignocellulose nanofibrils (LCNF), obtained from simple mechanical fibrillation of wood, are proposed as a source of continuous carbon microfibers obtained by wet spinning followed by single-step carbonization at 900 °C. The high lignin content of LCNF (∼28% based on dry mass), similar to that of the original wood, allowed the synthesis of carbon microfibers with a high carbon yield (29%) and electrical conductivity (66 S cm).

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

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.

Protein Structure Analysis and Validation with X-Ray Crystallography.

X-ray crystallography is the main technique for the determination of protein structures. About 85% of all protein structures known to date have been elucidated using X-ray crystallography. Knowledge of the three-dimensional structure of proteins can be used in various applications in biotechnology, biomedicine, drug design , and basic research and as a validation tool for protein modifications and ligand binding.

The SARS-CoV-2 Spike Glycoprotein as a Drug and Vaccine Target: Structural Insights into Its Complexes with ACE2 and Antibodies.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the Coronavirus disease (COVID-19) pandemic, has so far resulted in more than 1.1 M deaths and 40 M cases worldwide with no confirmed remedy yet available. Since the first outbreak in Wuhan, China in December 2019, researchers across the globe have been in a race to develop therapies and vaccines against the disease.

The binding mechanism of the virulence factor adhesin P subtype to globotetraosylceramide is associated with systemic disease.

is part of the pig commensal microbiome but strains can also be pathogenic, causing pneumonia and meningitis in pigs as well as zoonotic meningitis. According to genomic analysis, is divided into asymptomatic carriage, respiratory and systemic strains with distinct genomic signatures. Because the strategies to target pathogenic are limited, new therapeutic approaches are needed.

The Interaction of the Microtubule Targeting Anticancer Drug Colchicine with Human Glutathione Transferases.

Background: Glutathione transferases (GSTs) are a family of Phase II detoxification enzymes that have been shown to be involved in the development of multi-drug resistance (MDR) mechanism toward chemotherapeutic agents. GST inhibitors have, therefore, emerged as promising chemosensitizers to manage and reverse MDR. Colchicine (COL) is a classical antimitotic, tubulin-binding agent (TBA) which is being explored as anticancer drug.

The Interaction of Glutathione Transferase with Cibacron Blue 3GA and its Fragments.

Background: The 26kDa glutathione transferase (GST, EC 2.5.1.

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

Multiple-herbicide resistant (MHR) weeds are a global problem and a looming threat to weed control in crops. MHR weeds express a specific phi class glutathione transferase (MHR-GSTF) which seems to contribute to herbicide resistance. The present work aims to investigate the structure and catalytic properties of the MHR-GSTFs from different grass weeds and crops (Alopecurus myosuroides, Lolium rigidum, Hordeum vulgare, Triticum aestivum).

PDE6D Inhibitors with a New Design Principle Selectively Block K-Ras Activity.

The trafficking chaperone PDE6D (also referred to as PDEδ) has been nominated as a surrogate target for K-Ras4B (hereafter K-Ras). Arl2-assisted unloading of K-Ras from PDE6D in the perinuclear area is significant for correct K-Ras localization and therefore activity. However, the unloading mechanism also leads to the undesired ejection of PDE6D inhibitors.

Crystal Structure of a GH3 β-Glucosidase from the Thermophilic Fungus .

Beta-glucosidases (β-glucosidases) have attracted considerable attention in recent years for use in various biotechnological applications. They are also essential enzymes for lignocellulose degradation in biofuel production. However, cost-effective biomass conversion requires the use of highly efficient enzymes.

Effects of non-solvents and electrolytes on the formation and properties of cellulose I filaments.

Coagulation is a critical process in the assembly of cellulose nanofibrils into filaments by wet spinning; however, so far, the role of the coagulation solvent has not been systematically elucidated in this context. This work considers organic non-solvents (ethanol, acetone) and aqueous electrolyte solutions (NaCl(aq), HCl(aq), CaCl(aq)) for the coagulation of negatively charged cellulose nanofibrils via wet spinning. The associated mechanisms of coagulation with such non-solvents resulted in different spinnability, coagulation and drying time.