Hexahelicene DNA-binding: Minor groove selectivity, semi-intercalation and chiral recognition.

In this contribution, we focused on a fundamental study targeting the interaction of water-soluble [6]helicene derivative 1 (1-butyl-3-(2-methyl[6]helicenyl)-imidazolium bromide) with double-stranded (ds) DNA. A synthetic 30-base pair duplex, plasmid, chromosomal calf thymus and salmon DNA were investigated using electrochemistry, electrophoresis and spectroscopic tools supported by molecular dynamics (MD) and quantum mechanical approaches. Both experimental and theoretical work revealed the minor groove binding of 1 to the dsDNA.

Unique peptidic agonists of a juvenile hormone receptor with species-specific effects on insect development and reproduction.

Juvenile hormones (JHs) control insect metamorphosis and reproduction. JHs act through a receptor complex consisting of methoprene-tolerant (Met) and taiman (Tai) proteins to induce transcription of specific genes. Among chemically diverse synthetic JH mimics (juvenoids), some of which serve as insecticides, unique peptidic juvenoids stand out as being highly potent yet exquisitely selective to a specific family of true bugs.

Explaining the interaction of mangiferin with MMP-9 and NF-ƙβ: a computational study.

Mangiferin is a glycosylated xanthone widely distributed in nature, which exhibits wide pharmacological activities, highlighting its anti-cancer properties. Mangiferin interferes with inflammation, lipid, and calcium signaling, which selectively inhibits multiple NFkB target genes as interleukin-6, tumor necrosis factor, plasminogen, and matrix metalloproteinase, among others. In this work, the interactions of this polyphenol with MMP-9 and NF-κβ are characterized by using computational chemistry methods.

Mechanistic insight into the RNA-stimulated ATPase activity of tick-borne encephalitis virus helicase.

The helicase domain of nonstructural protein 3 (NS3H) unwinds the double-stranded RNA replication intermediate in an ATP-dependent manner during the flavivirus life cycle. While the ATP hydrolysis mechanism of Dengue and Zika viruses NS3H has been extensively studied, little is known in the case of the tick-borne encephalitis virus NS3H. We demonstrate that ssRNA binds with nanomolar affinity to NS3H and strongly stimulates the ATP hydrolysis cycle, whereas ssDNA binds only weakly and inhibits ATPase activity in a noncompetitive manner.

Specific anion effect on properties of HRV 3C protease.

Specific salts effect is intensively studied from the prospective of modification of different physico-chemical properties of biomacromolecules. Limited knowledge of the specific salts effect on enzymes led us to address the influence of five sodium anions: sulfate, phosphate, chloride, bromide, and perchlorate, on catalytic and conformational properties of human rhinovirus-14 (HRV) 3C protease. The enzyme conformation was monitored by circular dichroism spectrum (CD) and by tyrosines fluorescence.

Metallic Effects on p-Hydroxyphenyl Porphyrin Thin-Film-Based Planar Optical Waveguide Gas Sensor: Experimental and Computational Studies.

Metal effects on the gas sensing behavior of metal complexes of 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (THPP) thin film was investigated in terms of detecting NO gas by the planar optical waveguide. For this purpose, several THPP and metal complexes were synthesized with different central metal ions: Co(II), Ni(II), Cu(II), and Zn(II). Planar optical gas sensors were fabricated with the metalloporphyrins deposited on K ion-exchanged soda-lime glass substrate with the spin coating method serving as host matrices for gas interaction.

Interactions between a dsDNA Oligonucleotide and Imidazolium Chloride Ionic Liquids: Effect of Alkyl Chain Length, Part I.

Ionic liquids (ILs) have become nearly ubiquitous solvents and their interactions with biomolecules has been a focus of study. Here, we used the fluorescence emission of DAPI, a groove binding fluorophore, coupled with molecular dynamics (MD) simulations to report on interactions between imidazolium chloride ([Im]) ionic liquids and a synthetic DNA oligonucleotide composed entirely of T/A bases (7(TA)) to elucidate the effects ILs on a model DNA duplex. Spectral shifts on the order of 500-1000 cm, spectral broadening (~1000 cm), and excitation and emission intensity ratio changes combine to give evidence of an increased DAPI environment heterogeneity on added IL.

Computational and experimental assessment of pH and specific ions on the solute solvent interactions of clay-biochar composites towards tetracycline adsorption: Implications on wastewater treatment.

Experimental and computational investigations have been conducted in this study to assess the influence of municipal waste pyrolyzed biochar impregnated clay composites on antibiotic removal as a material for wastewater treatment and simultaneous value-addition for waste. The surface potential (zeta potential) of the pristine biochar and composite samples are found to be within the range ~10 to ~ -40 mV in the pH range 2-10. The presence of different inorganic salt solutions influences the electrophoretic mobility of the dispersed phase in a suspension, as well as its zeta potential.

Substituent Effect on Porphyrin Film-Gas Interaction by Optical Waveguide: Spectrum Analysis and Molecular Dynamic Simulation.

Substituent effect on optical gas sensing performance in porphyrin-based optical waveguide detection system was studied by molecular dynamics simulation (MDS), absorption/emission spectrum analysis, and optical waveguide (OWG) detection. The affinities of porphyrin with seven types of substituents (-H, -OH, -tBu, -COOH, -NH, -OCH, -SO) on para position of meso-phenyl porphyrin toward gas molecules in adsorption process were studied in different size of boxes with the same pressure and concentration. Analyte gases (CO, HS, HCl, NO) were exposed to porphyrin film in absorption spectrophotometer, and in OWG with evanescent field excited by a guiding laser light with 670 nm wavelength.

Conserved Dynamic Mechanism of Allosteric Response to L-arg in Divergent Bacterial Arginine Repressors.

Hexameric arginine repressor, ArgR, is the feedback regulator of bacterial L-arginine regulons, and sensor of L-arg that controls transcription of genes for its synthesis and catabolism. Although ArgR function, as well as its secondary, tertiary, and quaternary structures, is essentially the same in and , the two proteins differ significantly in sequence, including residues implicated in the response to L-arg. Molecular dynamics simulations are used here to evaluate the behavior of intact ArgR with and without L-arg, and are compared with prior MD results for a domain fragment of ArgR.

A residue of motif III positions the helicase domains of motor subunit HsdR in restriction-modification enzyme EcoR124I.

Type I restriction-modification enzymes differ significantly from the type II enzymes commonly used as molecular biology reagents. On hemi-methylated DNAs type I enzymes like the EcoR124I restriction-modification complex act as conventional adenine methylases at their specific target sequences, but unmethylated targets induce them to translocate thousands of base pairs through the stationary enzyme before cleaving distant sites nonspecifically. EcoR124I is a superfamily 2 DEAD-box helicase like eukaryotic double-strand DNA translocase Rad54, with two RecA-like helicase domains and seven characteristic sequence motifs that are implicated in translocation.

Aggregation and metal-complexation behaviour of THPP porphyrin in ethanol/water solutions as function of pH.

The effect of pH change on 5,10,15,20-Tetrakis(4-hydroxyphenyl)-21H,23H-porphine (THPP) with its aggregation as function of water-ethanol mixture was studied with UV-vis, fluorescence, Raman and computational analysis. In neutral pH, THPP was present as free-base and, increasing the water amount, aggregation occurred with the formation of H- and J-aggregates. The aggregation constant and the concentration of dimers were calculated, other information about the dimer aggregation were evaluated by computational study.

Transmembrane helix connectivity in Orai1 controls two gates for calcium-dependent transcription.

The channel Orai1 requires Ca store depletion in the endoplasmic reticulum and an interaction with the Ca sensor STIM1 to mediate Ca signaling. Alterations in Orai1-mediated Ca influx have been linked to several pathological conditions including immunodeficiency, tubular myopathy, and cancer. We screened large-scale cancer genomics data sets for dysfunctional Orai1 mutants.

Theoretical and experimental study of the antifreeze protein AFP752, trehalose and dimethyl sulfoxide cryoprotection mechanism: correlation with cryopreserved cell viability.

In this work the physico-chemical properties of selected cryoprotectants (antifreeze protein TrxA-AFP752, trehalose and dimethyl sulfoxide) were correlated with their impact on the constitution of ice and influence on frozen/thawed cell viability. The freezing processes and states of investigated materials solutions were described and explained from a fundamental point of view using ab-initio modelling (molecular dynamics, DFT), Raman spectroscopy, Differential Scanning Calorimetry and X-Ray Diffraction. For the first time, in this work we correlated the microscopic view (modelling) with the description of the frozen solution states and put these results in the context of human skin fibroblast viability after freezing and thawing.

The mechanism of the glycosylase reaction with hOGG1 base-excision repair enzyme: concerted effect of Lys249 and Asp268 during excision of 8-oxoguanine.

The excision of 8-oxoguanine (oxoG) by the human 8-oxoguanine DNA glycosylase 1 (hOGG1) base-excision repair enzyme was studied by using the QM/MM (M06-2X/6-31G(d,p):OPLS2005) calculation method and nuclear magnetic resonance (NMR) spectroscopy. The calculated glycosylase reaction included excision of the oxoG base, formation of Lys249-ribose enzyme-substrate covalent adduct and formation of a Schiff base. The formation of a Schiff base with ΔG# = 17.

The helical domain of the EcoR124I motor subunit participates in ATPase activity and dsDNA translocation.

Type I restriction-modification enzymes are multisubunit, multifunctional molecular machines that recognize specific DNA target sequences, and their multisubunit organization underlies their multifunctionality. EcoR124I is the archetype of Type I restriction-modification family IC and is composed of three subunit types: HsdS, HsdM, and HsdR. DNA cleavage and ATP-dependent DNA translocation activities are housed in the distinct domains of the endonuclease/motor subunit HsdR.

Quantum Calculations Indicate Effective Electron Transfer between FMN and Benzoquinone in a New Crystal Structure of Escherichia coli WrbA.

Unlabelled: Quantum mechanical calculations using the Marcus equation are applied to compare the electron-transfer probability for two distinct crystal structures of the Escherichia coli protein WrbA, an FMN-dependent

Nad(p)h: quinone oxidoreductase, with the bound substrate benzoquinone. The calculations indicate that the position of benzoquinone in a new structure reported here and solved at 1.33 Å resolution is more likely to be relevant for the physiological reaction of WrbA than a previously reported crystal structure in which benzoquinone is shifted by ∼5 Å.

Influence of ligand binding on structure and thermostability of human α1-acid glycoprotein.

Ligand binding of neutral progesterone, basic propranolol, and acidic warfarin to human α1-acid glycoprotein (AGP) was investigated by Raman spectroscopy. The binding itself is characterized by a uniform conformational shift in which a tryptophan residue is involved. Slight differences corresponding to different contacts of the individual ligands inside the β-barrel are described.

Molecular dynamics comparison of E. coli WrbA apoprotein and holoprotein.

WrbA is a novel multimeric flavodoxin-like protein of unknown function. A recent high-resolution X-ray crystal structure of E. coli WrbA holoprotein revealed a methionine sulfoxide residue with full occupancy in the FMN-binding site, a finding that was confirmed by mass spectrometry.

Interdomain communication in the endonuclease/motor subunit of type I restriction-modification enzyme EcoR124I.

Restriction-modification systems protect bacteria from foreign DNA. Type I restriction-modification enzymes are multifunctional heteromeric complexes with DNA-cleavage and ATP-dependent DNA translocation activities located on endonuclease/motor subunit HsdR. The recent structure of the first intact motor subunit of the type I restriction enzyme from plasmid EcoR124I suggested a mechanism by which stalled translocation triggers DNA cleavage via a lysine residue on the endonuclease domain that contacts ATP bound between the two helicase domains.

Binding-competent states for L-arginine in E. coli arginine repressor apoprotein.

Arginine repressor of E. coli is a multifunctional hexameric protein that provides feedback regulation of arginine metabolism upon activation by the negatively cooperative binding of L-arginine. Interpretation of this complex system requires an understanding of the protein's conformational landscape.

1.2 Å resolution crystal structure of Escherichia coli WrbA holoprotein.

The Escherichia coli protein WrbA, an FMN-dependent NAD(P)H:quinone oxidoreductase, was crystallized under new conditions in the presence of FAD or the native cofactor FMN. Slow-growing deep yellow crystals formed with FAD display the tetragonal bipyramidal shape typical for WrbA and diffract to 1.2 Å resolution, the highest yet reported.

Biphasic kinetic behavior of E. coli WrbA, an FMN-dependent NAD(P)H:quinone oxidoreductase.

The E. coli protein WrbA is an FMN-dependent NAD(P)H:quinone oxidoreductase that has been implicated in oxidative defense. Three subunits of the tetrameric enzyme contribute to each of four identical, cavernous active sites that appear to accommodate NAD(P)H or various quinones, but not simultaneously, suggesting an obligate tetramer with a ping-pong mechanism in which NAD departs before oxidized quinone binds.