Antibiotic metabolites and antimicrobial peptides mediate competition between bacterial species. Many of them hijack inner and outer membrane proteins to enter cells. Sensitivity of enteric bacteria to multiple peptide antibiotics is controlled by the single inner membrane protein SbmA. To establish the molecular mechanism of peptide transport by SbmA and related BacA, we determined their cryo-electron microscopy structures at 3.2 and 6 Å local resolution, respectively. The structures show a previously unknown fold, defining a new class of secondary transporters named SbmA-like peptide transporters. The core domain includes conserved glutamates, which provide a pathway for proton translocation, powering transport. The structures show an outward-open conformation with a large cavity that can accommodate diverse substrates. We propose a molecular mechanism for antibacterial peptide uptake paving the way for creation of narrow-targeted therapeutics.
Under limiting sulfur availability, bacteria can assimilate sulfur from alkanesulfonates. Bacteria utilize ATP-binding cassette (ABC) transporters to internalise them for further processing to release sulfur. In gram-negative bacteria the TauABC and SsuABC ensure internalization, although, these two systems have common substrates, the former has been characterized as a taurine specific system. TauA and SsuA are substrate-binding proteins (SBPs) that bind and bring the alkanesulfonates to the ABC importer for transport. Here, we have determined the crystal structure of TauA and have characterized its thermodynamic binding parameters by isothermal titration calorimetry in complex with taurine and different alkanesulfonates. Our structures revealed that the coordination of the alkanesulfonates is conserved, with the exception of Asp205 that is absent from SsuA, but the thermodynamic parameters revealed a very high enthalpic penalty cost for binding of the other alkanesulfonates relative to taurine. Our molecular dynamic simulations indicated that the different levels of hydration of the binding site contributed to the selectivity for taurine over the other alkanesulfonates. Such selectivity mechanism is very likely to be employed by other SBPs of ABC transporters.
Crystallizations in uranyl-containing ionic liquids yielding crystals {X} a {[UO 2 ] b [Y] c } with selected anions and cations (X = [Bmim] + for Y = Cl − , NO 3 − , and SCN − ; Y = Cl − for X = [Emim] + , [Emmim] + , [Bmim] + , and [Bmmim] + ;Emim = l-ethyl-3-methyl-imidazolium, Emmim = l-ethyl-2,3-dimethylimidazolium, Bmim = l-butyl-3-methylimidazolium, and Bmmim = l-butyl-2,3-dimethylimidazolium) were performed herein. Through standard crystallographic analyses, Hirshfeld surface analyses, and multiple characterization techniques, compounds with common cations/anions were investigated. For compounds [Bmim] 2 [(UO 2 ) 2 (μ-OH) 2 (NO 3 ) 4 ] (1), [Bmim] 3 [UO 2 (NCS) 5 ] (2), and [Bmim] 2 [UO 2 Cl 4 ] (3TT and 3TG), common [Bmim] + cations with different conformations were studied with respect to packing and interactions (for 1). The coordinated [(UO 2 ) 2 (μ-OH) 2 (NO 3 ) 4 ] 2− , [UO 2 (NCS) 5 ] 3− , and [UO 2 Cl 4 ] 2− anions that have historically been related to nuclear fuel cycles were demonstrated with respect to geometry and distortion. For compounds with common [UO 2 Cl 4 ] 2− anions [Emim] 2 [UO 2 Cl 4 ] (4), [Emmim] 2 [UO 2 Cl 4 ] (5), [Bmmim] 2 [UO 2 Cl 4 ] (6), 3TT, and 3TG, observed interionic interactions that have been previously impeded by limited structural information were discussed fully in relation to different cations and temperatures. Moreover, multistep phase transformations of 2, which have been undefined in solution studies, have been identified through differential scanning calorimetry analyses and polarizing optical microscopy. The polymorph transformations between 3TT and 3TG in solution, as controlled by uranyl concentration, were studied using optical microscopy and powder X-ray diffraction. The thermal stability, IR/Raman, and UV−vis/luminescence spectra of these compounds were also investigated. ■ INTRODUCTIONIonic liquids (ILs) are attractive to investigators due to their unique physical and chemical properties and have thus been widely examined in many areas. 1,2 Among their usages, crystallization in ILs is a complex and fascinating field of research. 3−5 Both the unique coordination features that cannot generally be observed using molecular solvents and the interaction specifics that are difficult to obtain in the liquid state of ILs can be investigated. 6,7 However, the crystallography data that have immensely promoted our understanding of intermolecular interactions 8 have not been fully explored regarding the crystallographic potential in IL systems.A special interest in f metal-containing ILs has recently arisen in various fields, resulting in many high-quality investigations involving crystallographic studies. 9−12 Specifically, promising applications of ILs in nuclear fuel cycles 13−17 have encouraged extensive studies on uranium-based IL systems, including the relatively common crystallization of uranium salts in ILs and novel explorations of crystallization methods in such complex systems. [3][4][5][6]13,18,19 Using the widely studied uranyl-imidazolium structures as...
Spatiotemporal controllable siRNA delivery and gene modulation by light-triggerable aptamer nanoswitcher was reported in this study, which achieved on-demand siRNA internalization by cancer cells at desired site and time in vitro and in vivo.
Polychloride ionic liquids can not only successfully dissolve UO2, but also raise the chlorine efficiency.
The glucose transporter 4 (GLUT4) plays a key role in maintaining whole body glucose homeostasis. Tracking GLUT4 in space and time can provide new insights for understanding the mechanisms of insulin-regulated GLUT4 translocation. Organic dyes and fluorescent proteins were used in previous studies for investigating the traffic of GLUT4 in skeletal muscle cells and adipocytes. Because of their relative weak fluorescent signal against strong cellular autofluorescence background and their fast photobleaching rate, most studies only focused on particular segments of GLUT4 traffic. In this study, we have developed a new method for observing the translocation of GLUT4 targeted with photostable and bright quantum dots (QDs) in live L6 cells. QDs were targeted to GLUT4myc specifically and internalized with GLUT4myc through receptor-mediated endocytosis. Compared with traditional fluorescence dyes and fluorescent proteins, QDs with high brightness and extremely photostability are suitable for long-term single particle tracking, so individual GLUT4-QD complex can be easily detected and tracked for long periods of time. This newly described method will be a powerful tool for observing the translocation of GLUT4 in live L6 cells.
Systems containing 1-alkyl-3-methylimidazolium chloride ionic liquid and chlorine gas were investigated. Using relativistic density functional theory, we calculated the formation mechanism of trichloride and hydrogen dichloride anions in an Emim(+)Cl(-) + Cl(2) system. Emim(+)Cl(3)(-) forms without energy barriers. The more stable species ClEmim(+)HCl(2)(-) forms through chlorine substitution. Substitution of a H on the imidazolium ring is much easier than substitution on the alkyl side chains. Infrared, Raman, ESI-MS, and (1)H NMR spectra were measured for EmimCl, BmimCl, and DmimCl with and without Cl(2) gas. The coexistence of Cl(3)(-) and HCl(2)(-), as well as chlorine-substituted cations, was confirmed by detection of their spectroscopic signals in the Cl(2) added ionic liquids. Cl substitution appears less serious for cations with longer side chains.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.