Fungal Plasma Membrane H+-ATPase: Structure, Mechanism, and Drug Discovery.

The fungal plasma membrane H+-ATPase (Pma1) pumps protons out of the cell to maintain the transmembrane electrochemical gradient and membrane potential. As an essential P-type ATPase uniquely found in fungi and plants, Pma1 is an attractive antifungal drug target. Two recent Cryo-EM studies on Pma1 have revealed its hexameric architecture, autoinhibitory and activation mechanisms, and proton transport mechanism. These structures provide new perspectives for the development of antifungal drugs targeting Pma1. In this article, we review the history of Pma1 structure determination, the latest structural insights into Pma1, and drug discoveries targeting Pma1.

Structure of a fungal 1,3-ß-glucan synthase.

1,3-ß-Glucan serves as the primary component of the fungal cell wall and is produced by 1,3-ß-glucan synthase located in the plasma membrane. This synthase is a molecular target for antifungal drugs such as echinocandins and the triterpenoid ibrexafungerp. In this study, we present the cryo-electron microscopy structure of Saccharomyces cerevisiae 1,3-ß-glucan synthase (Fks1) at 2.47-Å resolution. The structure reveals a central catalytic region adopting a cellulose synthase fold with a cytosolic conserved GT-A-type glycosyltransferase domain and a closed transmembrane channel responsible for glucan transportation. Two extracellular disulfide bonds are found to be crucial for Fks1 enzymatic activity. Through structural comparative analysis with cellulose synthases and structure-guided mutagenesis studies, we gain previously unknown insights into the molecular mechanisms of fungal 1,3-ß-glucan synthase.

[Adsorption of As(â ¢) in Water by Iron-loaded Graphene Oxide-Chitosan].

Based on the principle of self-assembly, graphene oxide, chitosan, and FeCl3·6H2O were mixed to prepare graphene oxide-chitosan coated iron-composite particles (Fe@ GOCS). Batch static experiments were carried out to investigate the kinetic and thermodynamic characteristics of As(Ⅲ) adsorption, and to identify the adsorption mechanism. Results showed that the iron on the GOCS was mainly in the form of α-FeO(OH). The As(Ⅲ) adsorption capacity increased with decreasing pH, and the highest adsorption capacity occurred at pH 3. After approximately 45 h, As(Ⅲ) adsorption reached equilibrium under the conditions of pH 3 and a temperature of 298.15, 308.15, and 318.15 K. The maximum adsorption capacity was 289.4 mg·g-1 for an optimal dosage of adsorbents of 1.0 g·L-1. After five times of repeated adsorption-desorption, the adsorption capacity increased slightly. The thermodynamic parameters showed that ΔGθ<0, ΔSθ > 0, and ΔHθ>0, thus indicating that As(Ⅲ) adsorption on Fe@GOCS was a spontaneous, endothermic, and entropy-increasing reaction, and that a higher temperature was more favorable for As(Ⅲ) adsorption. The pseudo-second-order model provided a good fit of the As(Ⅲ) adsorption kinetics for Fe@GOCS. Compared to the Langmuir isotherm, As(Ⅲ) adsorption experimental data fitted better to the Freundlich and Sips models. In combination with the characterization results, it was found that ion exchange and surface complexation were the main mechanisms of As(Ⅲ) removal from aqueous solution using Fe@GOCS.

[Characteristics and Influencing Factors of Monothioarsenate Adsorption on Goethite].

The adsorption kinetic of monothioarsenate (MTA) on goethite was characterized in this study, and batch experiments were then designed to further explore the effects of arsenate, arsenite, humic acid (HA), nitrate, and phosphate on the adsorption of MTA on goethite, and to identify the adsorption mechanism. The results showed that:① When a single arsenic species was present in a solution, the adsorption equilibrium times of MTA, arsenate, and arsenite on goethite were 8, 2, and 4 h, respectively. The adsorption experimental data of these three arsenic species were well fitted to a pseudo-second-order kinetic model. The equilibrium adsorption capacities (qe) of MTA, arsenate, and arsenite on goethite were 2129.851, 3291.838, and 1788.767 mg·kg-1, respectively. When MTA coexisted with arsenate or arsenite in a solution, MTA adsorption on goethite continued to be well fitted to a pseudo-second-order kinetic model. The value of qe for MTA was significantly reduced to 1236.941 mg·kg-1 when MTA coexisted with arsenate, and to 1532.287 mg·kg-1 when MTA coexisted with arsenite, due to the fact that arsenate and arsenite competed for adsorption sites with MTA. ② With an increase in HA concentration (10-50 mg·L-1), the qe of MTA decreased gradually, due to the fact that a large number of functional groups in HA preempted the surface adsorption sites of goethite with MTA. ③ When phosphate was added into the MTA solution, the qe values of MTA, arsenate, and arsenite on goethite were reduced greatly, to 492.802, 815.782, and 303.714 mg·kg-1, respectively, which was caused by the competitive adsorption of P and As. When nitrate was added into the MTA solution, the number of electron receptors and Eh of the solution increased, leading to the qe values of MTA, arsenate, and arsenite on goethite increasing to 2211.030, 3444.023, and 1835.537 mg·kg-1, respectively.

[Characteristics and Mechanism of Monothioarsenate Adsorption on Sand, Sediment, and Goethite].

Batch experiments were conducted to investigate the adsorption characteristics and mechanism of monothioarsenate (MTA) (>99%) on sand, soil sediment, and goethite under different pH and solid-liquid ratio conditions. Results showed the following. ① When MTA ranged from 0.14 to 23.59, 0.19 to 41.27, and 0.27 to 32.02 mg·L-1 in solutions, its maximum equilibrium adsorption capacity (Qm) in sand, soil sediment, and goethite was 21.54, 277.98, and 2607.42 mg·kg-1, respectively. After its adsorption reached equilibrium, a small amount of the MTA in the solutions transformed into arsenite and arsenate. ② As pH increased from 4 to 10, the equilibrium adsorption capacity (Qe) of MTA on sand decreased gradually, whereas Qe first decreased and then increased for soil sediment and goethite. As the solid-liquid ratio increased, the Qe of MTA in the three media gradually decreased. ③ X-ray powder diffraction (XRD), scanning electron microscope (SEM), and BET results further showed that the major factors controlling MTA adsorption on the three media included the low pore volume of sand, the high degree of crystallization of the soil sediment, and the large number of hydroxyl functional groups (-OH) on goethite.

Luteimonas soli sp. nov., isolated from farmland soil.

A yellow-pigmented bacterial strain, designated Y2T, was isolated from farmland soil in Bengbu, Anhui province, China. Cells of strain Y2T were Gram-stain-negative, strictly aerobic, non-motile and rod-shaped. Strain Y2T grew optimally at pH 7.0, 30 °C and in the presence of 2 % (w/v) NaCl. The DNA G+C content was 68.9 mol%. The major fatty acids (>5 %) were iso-C15 : 0, iso-C17 : 0, summed feature 9 (C16 : 0 10-methyl and/or iso-C17 : 1ω9c), iso-C11 : 0 3-OH and iso-C11 : 0. The major respiratory quinone was ubiquinone-8 (Q-8), and the major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Phylogenetic analysis of the 16S rRNA gene sequences showed that strain Y2T was most closely related to Luteimonas mephitis B1953/27.1T (99.1 % 16S rRNA gene sequence similarity), followed by Luteimonas lutimaris G3T (98.6 %), Luteimonas abyssi XH031T (96.2 %) and Luteimonas aquatica RIB1-20T (96.0 %). Strain Y2T exhibited low DNA-DNA relatedness with Luteimonas mephitis B1953/27.1T (43.6 ± 0.5 %) and Luteimonas lutimaris G3T (43.9 ± 2.1 %). On the basis of phenotypic, genotypic and phylogenetic evidence, strain Y2T represents a novel species of the genus Luteimonas, for which the name Luteimonas soli sp. nov. is proposed. The type strain is Y2T ( = ACCC 19799T = KCTC 42441T).