Volume 17, Issue 1, March - December 2024
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Bacterial Glycolipid Acting on Protein Transport across Membranes
The process of protein transport across membranes involves a variety of factors and has been extensively investigated. Traditionally, proteinaceous translocons and chaperones have been recognized as crucial factors in this process. However, recent studies have highlighted the significant roles played by lipids and a glycolipid present in biological membranes in membrane protein transport. Membrane lipids can influence transport efficiency by altering the physicochemical properties of membranes. Notably, our studies have revealed that diacylglycerol (DAG) attenuates mobility in the membrane core region, leading to a dramatic suppression of membrane protein integration. Conversely, a glycolipid in Escherichia coli inner membranes, named membrane protein integrase (MPIase), enhances integration not only through the alteration of membrane properties but also via direct interactions with membrane proteins. This review explores the mechanisms of membrane protein integration mediated by membrane lipids, specifically DAG, and MPIase. Our results, along with the employed physicochemical analysis methods such as fluorescence measurements, nuclear magnetic resonance, surface plasmon resonance, and docking simulation, are presented to elucidate these mechanisms.
Design, synthesis and antibacterial evaluation of N-Substituted indole derivatives containing 1,3,4-thiadiazole and amide moieties
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Exploring a Solvent Dependent Strategy to Control Self‐Assembling Behavior and Cellular Interaction in Laminin‐Mimetic Short Peptide based Supramolecular Hydrogels
Self-assembled hydrogels, fabricated through diverse non-covalent interactions, have been extensively studied in regenerative medicines. Inspired from bioactive functional motifs of ECM protein, short peptide sequences have shown remarkable abilities to replicate the intrinsic features of the natural extracellular milieu. In this direction, we have fabricated two short hydrophobic bioactive sequences derived from the laminin protein i.e., IKVAV and YIGSR. Based on the substantial hydrophobicity of these peptides, we selected a co-solvent approach as a suitable gelation technique that included different concentrations of DMSO as an organic phase along with an aqueous solution containing 0.1% TFA. These hydrophobic laminin-based bioactive peptides which had limited solubility in aqueous physiological environment showed significantly enhanced solubility with higher DMSO content in water. The enhanced solubility resulted in extensive intermolecular interactions that led to the formation of hydrogels with a higher-order entangled network along with improved mechanical properties. Interestingly, by simply modulating DMSO content, highly tunable gels were accessed in the same gelator domain that displayed differential physicochemical properties. Further, the cellular studies substantiated the potential of these laminin-derived hydrogels in enhancing cell-matrix interactions, thereby reinforcing their applications in tissue engineering.
Nonlinear impact of electrolyte solutions on protein dynamics
Halophilic organisms have adapted to multi-molar salt concentrations, their cytoplasmic proteins functioning despite stronger attraction between hydrophobic groups. These proteins, of interest in biotechnology because of decreasing fresh-water resources, have excess acidic amino acids. It has been suggested that conformational fluctuations -- critical for protein function -- decrease in the presence of a stronger hydrophobic effect, and that an acidic proteome would counteract this decrease. However, our understanding of the salt- and acidic amino acid dependency of enzymatic activity is limited. Here, using solution NMR relaxation and molecular dynamics simulations for in total 14 proteins, we show that salt concentration has a limited and moreover non-monotonic impact on protein dynamics. The results speak against the conformational-fluctuations model, instead indicating that maintaining protein dynamics to ensure protein function is not an evolutionary driving force behind the acidic proteome of halophilic proteins.
Uranium Cyanides from Reactions in Liquid Ammonia Solution
So far there are only very few uranium cyanides. Three novel uranium cyanides have been obtained from reactions of uranium halides with cyanides in liquid ammonia as a solvent.
Abstract
Reactions of uranium tri- and tetrahalides, UBr3, UI3, UCl4, and UI4, with different cyanides MCN (M=K, Ag) in liquid anhydrous ammonia led to three novel uranium(IV) cyanide compounds. The reaction of UCl4 in the presence of KCN resulted in the compound [U(CN)(NH3)8]Cl3 ⋅ 3NH3, while UBr3 and UI3 were oxidized in the presence of AgCN to form the compounds (μ-CN){(H3N)5U(μ-NH2)3U(NH3)5}]Br4 ⋅ 2NH3, and (μ-CN){(H3N)5U(μ-NH2)3U(NH3)5}]I4 ⋅ 2NH3. The reaction of UI4 with KCN in aNH3 also yielded the compound (μ-CN){(H3N)5U(μ-NH2)3U(NH3)5}]I4 ⋅ 2NH3. The compounds (μ-CN){(H3N)5U(μ-NH2)3U(NH3)5}]X 4 ⋅ 2NH3 (X=Br, I) crystallize in different space groups, Pmn21 (no. 31) and Imm2 (no. 44), respectively. In both cases, the (μ-CN){(H3N)5U(μ-NH2)3U(NH3)5}]4+ cation forms infinite strands. We conducted quantum-chemical calculations and Intrinsic Bond Orbital analyses on the observed [U(CN)(NH3)8]3+ cation and the [(μ-CN)2{(H3N)5U(μ-NH2)3U(NH3)5}]3+ model cation to gain insight into the bonding situation.
A DNA Force Circuit for Exploring Protein‐Protein Interactions at the Single‐Molecule Level†
A DNA force circuit was developed for detecting PPI anisotropy at the single-molecule level.
Comprehensive Summary
Protein-protein interactions (PPIs) play a crucial role in drug discovery and disease treatment. However, the development of effective drugs targeting PPIs remains challenging due to limited methodologies for probing their spatiotemporal anisotropy. Here, we propose a single-molecule approach using a unique force circuit to investigate PPI dynamics and anisotropy under mechanical forces. Unlike conventional techniques, this approach enables the manipulation and real-time monitoring of individual proteins at specific amino acids with defined geometry, offering insights into molecular mechanisms at the single-molecule level. The DNA force circuit was constructed using click chemistry conjugation methods and genetic code expansion techniques, facilitating orthogonal conjugation between proteins and nucleic acids. The SET domain of the MLL1 protein and the tail of histone H3 were used as a model system to demonstrate the application of the DNA force circuit. With the use of atomic force microscopy and magnetic tweezers, optimized assembly procedures were developed. The DNA force circuit provides an exceptional platform for studying the anisotropy of PPIs and holds promise for advancing drug discovery research targeted at PPIs.
Structural‐Functional Correlations between Unique N‐terminal Region and C‐terminal Conserved Motif in Short‐chain cis‐Prenyltransferase from Tomato
The cover shows the homodimeric neryl diphosphate synthase, a short-chaincis-prenyltransferase from tomato. The two active sites of the enzyme alternate in function, condensing two substrates on one site (represented by green tomatoes, front) while the other excretes the product (represented by red tomatoes, back). The conserved C-terminal motif of this enzyme changes its secondary structure during turnover and may, cooperatively with the unique N-terminal region, be important for the catalytic mechanism. More information can be found in the Research Article by S. Yamashita et al.
Cellular Metabolic Labeling of Nucleic Acids and Its Applications
Abstract
Nucleic acids are considered as fundamental molecules of living systems, which serve as universal genetic information messengers and repositories. To uncover the multifaceted aspects of nucleic acid function and metabolism within cells, labeling has become indispensable. This labeling technique enables the visualization, isolation, characterization, and even quantification of specific nucleic acid species. This review delves into cellular metabolic approaches for nucleic acid labeling, wherein enzymatic steps are employed to introduce nucleic acid modifications before conjugation with a label for detection or isolation. The discussion begins with metabolic labeling for DNA, RNA with various reactive groups and post-transcriptional RNA labeling for RNA methylation and acetylation sites, emphasizing recent advancements in the field and then, we spotlighted pertinent applications for cellular imaging and sequencing. of labeling.
Switchable Multicomponent Cyclization Reactions to Access Fluoroalkylated Dihydropyrimidines and Pyrimidines under Solvent‐Free Conditions
A switchable strategy for the construction of diverse 4-fluoroalkyl-1,4-dihydropyrimidines and 4-fluoroalkyl-pyrimidines via a solvent/additive-free [3 + 2 + 1] annulation, starting from readily available enamines, trifluoroacetaldehyde hydrate or 1-ethoxy-2,2-difluoroethanol and amidines hydrochloride has been developed.
Comprehensive Summary
The development of switchable solvent-free multicomponent reactions to build high-value-added products is an important demand for organic synthesis. Herein, we detailed the successful implementation of a switchable strategy for the construction of diverse 4-fluoroalkyl-1,4-dihydropyrimidines and 4-fluoroalkyl-pyrimidines via a solvent/additive-free [3 + 2 + 1] annulation, starting from readily available enamines, trifluoroacetaldehyde hydrate or 1-ethoxy-2,2-difluoroethanol and amidines hydrochloride. This reaction conforms to the concept of green synthesis, and provides a new avenue to access valuable fluorinated heterocycles.