Lysine Ethylation by Histone Lysine Methyltransferases.

Biomedicinally important histone lysine methyltransferases (KMTs) catalyze the transfer of a methyl group from S-adenosylmethionine (AdoMet) cosubstrate to lysine residues in histones and other proteins. Herein, experimental and computational investigations on human KMT-catalyzed ethylation of histone peptides by using S-adenosylethionine (AdoEth) and Se-adenosylselenoethionine (AdoSeEth) cosubstrates are reported. MALDI-TOF MS experiments reveal that, unlike monomethyltransferases SETD7 and SETD8, methyltransferases G9a and G9a-like protein (GLP) do have the capacity to ethylate lysine residues in histone peptides, and that cosubstrates follow the efficiency trend AdoMet>AdoSeEth>AdoEth.

Oligo (-Phenylene Vinylene)/Polyisocyanopeptide Biomimetic Composite Hydrogel-Based Three-Dimensional Cell Culture System for Anticancer and Antibacterial Therapeutics.

Cells are normally cultured in 2D environment, which is usually inconsistent with the real microenvironment in vivo, and it is rarely reported that an effective cancer cell killing process occurs in a 3D network environment. Herein, a kind of new biomimetic composite hydrogel which can achieve 3D cell culture has been prepared and constructed by assembly of polyisocyanopeptide (PIC) with cationic oligo (-phenylene vinylene) (OPV). The polymer chains of PIC can be bound and frizzled to form a 3D network when the temperature rises above the gelation temperature, followed by encapsulating the cells into biomimetic composite hydrogel.

Translation of bone wax and its substitutes: History, clinical status and future directions.

Bone wax, primarily composed of beeswax and softening agent, is a century-old material used to control bleeding of disrupted bone surfaces by acting as a mechanical barrier to seal the wound. The current bone wax products are commonly packed in easy-to-open foil in the form of sterile sticks or plates, with excellent malleability and smooth consistency, enabling cost-effective and easy handling approach for bleeding control. It has also been reported that the inert nature of bone wax causes complications including foreign body reaction, infection promotion and bone healing inhibition.

Antimicrobial Zn-Based "TSOL" for Citrus Greening Management: Insights from Spectroscopy and Molecular Simulation.

Huanglongbing (HLB), also known as citrus greening, is a bacterial disease that poses a devastating threat to the citrus industry worldwide. To manage this disease efficiently, we developed and characterized a ternary aqueous solution (TSOL) that contains zinc nitrate, urea, and hydrogen peroxide. We report that TSOL exhibits better antimicrobial activity than commercial bactericides for growers.

Sterile Lung Inflammation Induced by Silica Exacerbates Mycobacterium tuberculosis Infection via STING-Dependent Type 2 Immunity.

Lung inflammation induced by silica impairs host control of tuberculosis, yet the underlying mechanism remains unclear. Here, we show that silica-driven exacerbation of M. tuberculosis infection associates with raised type 2 immunity.

γ-Thialysine versus Lysine: An Insight into the Epigenetic Methylation of Histones.

Biomedicinally important histone lysine methyltransferases (KMTs) transfer a methyl group from S-adenosylmethionine to lysine residues in histones and other proteins. Here, we report comparative studies on epigenetic methylation of lysine and γ-thialysine, the simplest cysteine-derived lysine analog, which can be introduced to histone peptides and histone proteins via site-specific bioconjugation-based cysteine alkylation. Enzyme assays and computational studies demonstrate that human KMTs catalyze efficient methylation of histones that possess γ-thialysine.

Biosynthesis of methyl (E)-cinnamate in the liverwort Conocephalum salebrosum and evolution of cinnamic acid methyltransferase.

Methyl (E)-cinnamate is a specialized metabolite that occurs in a variety of land plants. In flowering plants, it is synthesized by cinnamic acid methyltransferase (CAMT) that belongs to the SABATH family. While rarely reported in bryophytes, methyl (E)-cinnamate is produced by some liverworts of the Conocephalum conicum complex, including C.

Imaging of extracellular cathepsin S activity by a selective near infrared fluorescence substrate-based probe.

We designed a near-infrared fluorescent substrate-based probe (SBP), termed MG101, for monitoring extracellular cathepsin S (CatS) activity. We conceived a fused peptide hairpin loop-structure, combining a CatS recognition domain, an electrostatic zipper (with complementary charges of a polyanionic (D-Glu) segment and a polycationic (D-Arg) motif, as well as a N and C terminal Förster resonance energy transfer pair (donor: AlexaFluor680; quencher: BHQ3) to facilitate activity-dependent imaging. MG101 showed excellent stability since no fluorescence release corresponding to a self-dequenching was observed in the presence of either 2 M NaCl or after incubation at a broad range of pH (2.

Addressing the Compartmentalization of Specific Integrin Heterodimers in Mouse Sperm.

Integrins are transmembrane cell receptors involved in two crucial mechanisms for successful fertilization, namely, mammalian intracellular signaling and cell adhesion. Integrins α6β4, α3β1 and α6β1 are three major laminin receptors expressed on the surface of mammalian cells including gametes, and the presence of individual integrin subunits α3, α6, β1 and β4 has been previously detected in mammalian sperm. However, to date, proof of the existence of individual heterodimer pairs in sperm and their detailed localization is missing.

Biological Membrane Organization and Cellular Signaling.

To execute their many vital functions, cell membranes are highly organized. Here, we review how membrane structure shapes signal transduction across membranes. Recent experimental and computational advances have shed significant light on mechanisms linking the function of membrane signaling proteins to the composition and physical properties of the membrane lateral structures in which they are embedded.

Ensemble Docking in Drug Discovery: How Many Protein Configurations from Molecular Dynamics Simulations are Needed To Reproduce Known Ligand Binding?

Ensemble docking in drug discovery or chemical biology uses dynamical simulations of target proteins to generate binding site conformations for docking campaigns. We show that 600 ns molecular dynamics simulations of four G-protein-coupled receptors in their membrane environments generate ensembles of protein configurations that, collectively, are selected by 70?99% of the known ligands of these proteins. Therefore, the process of ligand recognition by conformational selection can be reproduced by combining molecular dynamics and docking calculations.

Identification of Binding Sites for Efflux Pump Inhibitors of the AcrAB-TolC Component AcrA.

The overexpression of multidrug efflux pumps is an important mechanism of clinical resistance in Gram-negative bacteria. Recently, four small molecules were discovered that inhibit efflux in Escherichia coli and interact with the AcrAB-TolC efflux pump component AcrA. However, the binding site(s) for these molecules was not determined.

Environmental Mercury Chemistry - In Silico.

Mercury (Hg) is a global environmental contaminant. Major anthropogenic sources of Hg emission include gold mining and the burning of fossil fuels. Once deposited in aquatic environments, Hg can undergo redox reactions, form complexes with ligands, and adsorb onto particles.

Lipid Rafts: Buffers of Cell Membrane Physical Properties.

Lateral organization of lipids in the cell membrane appears to be an ancient feature of the cell, given the existence of lipid rafts in both eukaryotic and prokaryotic cells. Currently seen as platforms for protein partitioning, we posit that lipid rafts are capable of playing another role: stabilizing membrane physical properties over varying temperatures and other environmental conditions. Membrane composition defines the mechanical and viscous properties of the bilayer.

Quantum Mechanical/Molecular Mechanical Analysis of the Catalytic Mechanism of Phosphoserine Phosphatase.

Phosphoserine phosphatase (PSP), a member of the haloacid dehalogenase (HAD) superfamily that comprises the vast majority of phosphotransferases, is likely a steady-state regulator of the level of d-serine in the brain. The proposed catalytic cycle of PSP consists of a two-step mechanism: formation of a phospho-enzyme intermediate by phosphate transfer to Asp11 and its subsequent hydrolysis. Our combined quantum mechanical/molecular mechanical (QM/MM) calculations of the reaction pathways favour a dissociative mechanism of nucleophilic substitution via a trigonal-planar metaphosphate-like configuration for both steps, associated with proton transfer to the leaving group or from the nucleophile.

STING-dependent sensing of self-DNA drives silica-induced lung inflammation.

Silica particles induce lung inflammation and fibrosis. Here we show that stimulator of interferon genes (STING) is essential for silica-induced lung inflammation. In mice, silica induces lung cell death and self-dsDNA release in the bronchoalveolar space that activates STING pathway.

Synthesis by native chemical ligation and characterization of the scorpion toxin AmmTx3.

The scorpion toxin AmmTx3 is a specific blocker of K4 channels. It was shown to have interesting potential for neurological disorders. In this study, we report the first chemical synthesis of AmmTx3 by using the native chemical ligation strategy and validate its biological activity.

The importance of the membrane interface as the reference state for membrane protein stability.

The insertion of nascent polypeptide chains into lipid bilayer membranes and the stability of membrane proteins crucially depend on the equilibrium partitioning of polypeptides. For this, the transfer of full sequences of amino-acid residues into the bilayer, rather than individual amino acids, must be understood. Earlier studies have revealed that the most likely reference state for partitioning very hydrophobic sequences is the membrane interface.

Deletion in mice of X-linked, Brugada syndrome- and atrial fibrillation-associated Kcne5 augments ventricular K currents and predisposes to ventricular arrhythmia.

KCNE5 is an X-linked gene encoding KCNE5, an ancillary subunit to voltage-gated potassium (K) channels. Human KCNE5 mutations are associated with atrial fibrillation (AF)- and Brugada syndrome (BrS)-induced cardiac arrhythmias that can arise from increased potassium current in cardiomyocytes. Seeking to establish underlying molecular mechanisms, we created and studied Kcne5 knockout ( Kcne5) mice.

Remote-Controlling Potassium Channels in Living Cells through Photothermal Inactivation of Calmodulin.

Spatiotemporal regulation of cellular functions provides a powerful strategy for understanding underlying mechanisms of cellular bioprocesses. Here, a strategy is reported to realize the remote control of the activities of potassium channels via photothermal inactivation of calmodulin (CaM) by using reduced graphene oxide decorated with calmodulin binding peptide (rGO-P) as the transducer with near-infrared light (NIR) irradiation. Upon NIR light irradiation, the CaM/Ca bound to rGO-P is inactivated by the photothermal effect of rGO-P, resulting in the incapability of binding with Ca .

Dynamics of the lignin glass transition.

The dynamics of lignin, a complex and heterogeneous major plant cell-wall macromolecule, is of both fundamental and practical importance. Lignin is typically heated to temperatures above its glass transition to facilitate its industrial processing. We performed molecular dynamics simulations to investigate the segmental (α) relaxation of lignin, the dynamical process that gives rise to the glass transition.

A novel amphiphilic fluorescent probe BODIPY--CMC-cRGD as a biomarker and nanoparticle vector.

Fluorescent probes have been demonstrated to be promising candidates as biomarkers and biological carriers. Our study focuses on the development of a novel amphiphilic fluorescent probe with good photostability, high water solubility, excellent specificity and promising loading capability for tumor diagnosis and treatment. At first, BODIPY dye and -carboxymethyl chitosan were prepared a chemical reaction.