Structural and biophysical characterization of the cytoplasmic domains of HprS kinase and its interactions with the cognate regulator HprR.

The HprSR constitutes the bacterial two-component regulatory system engaged by Escherichia coli to reduce the damaging effects of reactive chlorine and oxygen species present in its cytosol. Hypochlorous acid (HOCl) has been shown to be the molecule capable of activating of the HprSR system. HOCl is produced upon pathogen invasion by phagocytic cells of the human innate immune system, particularly neutrophils, to take advantage of its powerful antimicrobial attributes.

Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids.

Mutant KRAS regulates transposable element (TE) RNA and interferon-stimulated gene (ISG) expression, but it remains unclear whether diverse mutations in KRAS affect different TE RNAs throughout the genome. We analyzed the transcriptomes of 3D human lung cancer spheroids that harbor KRAS(G12C) mutations to determine the landscape of TE RNAs regulated by mutant KRAS(G12C). We found that KRAS(G12C) signaling is required for the expression of LINE- and LTR-derived TE RNAs that are distinct from TE RNAs previously shown to be regulated by mutant KRAS(G12D) or KRAS(G12V).

Spectroscopy, molecular structure, and electropolymerization of Ni(II) and Cu(II) complexes containing a thiophene-appending fluorinated Schiff base ligand.

In this contribution, we describe the preparation, characterization, and electrochemical behavior of a series of four new mononuclear M(II) complexes featuring a symmetric substituted NO-tetradentate Schiff base ligand, bearing either trifluoromethyl and -bromophenyl (M = Ni, 3; Cu, 4) or trifluoromethyl and the π-extended -(2-thienyl)phenylene (M = Ni, 5; Cu, 6) substituents. Complexes 3 and 4 were readily synthesized by reacting the diprotic fluorinated Schiff base proligand 2 with the appropriate hydrated metal(II) acetates, whereas 5 and 6 were obtained upon Stille cross-coupling reaction of 3 and 4 with 2-(tributylstannyl)-thiophene, respectively. Compounds 3-6 were isolated as neutral, air, and thermally stable-coloured solids, with yields ranging from 60 to 80%.

Mutant KRAS regulates transposable element RNA and innate immunity via KRAB zinc-finger genes.

RAS genes are the most frequently mutated oncogenes in cancer, yet the effects of oncogenic RAS signaling on the noncoding transcriptome remain unclear. We analyzed the transcriptomes of human airway and bronchial epithelial cells transformed with mutant KRAS to define the landscape of KRAS-regulated noncoding RNAs. We find that oncogenic KRAS signaling upregulates noncoding transcripts throughout the genome, many of which arise from transposable elements (TEs).

Nickel(II)-Based Building Blocks with Schiff Base Derivatives: Experimental Insights and DFT Calculations.

We have recently reported a series of neutral square planar tridentate Schiff base (L) complexes of the general formula [(L)M(py)], showing relatively high first-order hyperpolarizabilities and NLO redox switching behavior. In the present study, new members of this family of compounds have been prepared with the objective to investigate their potential as building blocks in the on-demand construction of D-π-A push-pull systems. Namely, ternary nickel(II) building blocks of general formula [(L)Ni(4-pyX)] (), where L stands for an electron accepting or donating dianionic O,N,O-tridentate Schiff base ligand resulting from the monocondensation of 2-aminophenol or its 4-substituted nitro derivative and β-diketones R-C(=O)CHC(=O)CH (R = methyl, anisyl, ferrocenyl), and 4-pyX is 4-iodopyridine or 4-ethynylpyridine, were synthesized and isolated in 60-78% yields.

Functional analysis of four single (RGDWL, RGDWM, RGDWP, RGDMN) and two double (RGDNM, RGDMP) mutants: The importance of methionine (M) in the functional potency of recombinant mojastin (r-Moj).

We have demonstrated in previous studies that a single amino acid change can alter the activity of the recombinant disintegrin r-Moj. In this study, four r-Moj recombinants containing single mutations (r-Moj-WL, r-Moj-WM, r-Moj-WP, r-Moj-MN) and two containing double mutations (r-Moj-MP and r-Moj-NM) at the binding loop were produced, purified, and tested. All r-Moj-W_, r-Moj-M_, and r-Moj-NM mutant peptides inhibited platelet aggregation at higher potency than r-Moj-D_ mutants.

Functional characterization of six aspartate (D) recombinant mojastin mutants (r-Moj): A second aspartate amino acid carboxyl to the RGD in r-Moj-D_ peptides is not sufficient to induce apoptosis of SK-Mel-28 cells.

Disintegrins are small peptides produced in viper venom that act as integrin antagonists. When bound to integrins, disintegrins induce altered cellular behaviors, such as apoptotic induction. Disintegrins with RGDDL or RGDDM motifs induce apoptosis of normal and cancer cells.

Crystal structures of glutaminyl cyclases (QCs) from Drosophila melanogaster reveal active site conservation between insect and mammalian QCs.

Glutaminyl cyclases (QCs), which catalyze the formation of pyroglutamic acid (pGlu) at the N-terminus of a variety of peptides and proteins, have attracted particular attention for their potential role in Alzheimer's disease. In a transgenic Drosophila melanogaster (Dm) fruit fly model, oral application of the potent competitive QC inhibitor PBD150 was shown to reduce the burden of pGlu-modified Aβ. In contrast to mammals such as humans and rodents, there are at least three DmQC species, one of which (isoDromeQC) is localized to mitochondria, whereas DromeQC and an isoDromeQC splice variant possess signal peptides for secretion.

Kinetic and structural characterization of bacterial glutaminyl cyclases from Zymomonas mobilis and Myxococcus xanthus.

Although enzymes responsible for the cyclization of amino-terminal glutamine residues are present in both plant and mammal species, none have yet been characterized in bacteria. Based on low sequence homologies to plant glutaminyl cyclases (QCs), we cloned the coding sequences of putative microbial QCs from Zymomonas mobilis (ZmQC) and Myxococcus xanthus (MxQC). The two recombinant enzymes exhibited distinct QC activity, with specificity constants k(cat)/K(m) of 1.

Synthesis, spectral, structural, second-order nonlinear optical properties and theoretical studies on new organometallic donor-acceptor substituted nickel(II) and copper(II) unsymmetrical Schiff-base complexes.

The synthesis, spectroscopic and structural characterization, linear and nonlinear optical properties, as well as the electrochemical behavior of a series of robust neutral binuclear M[Fc-C(O)CH=C(CH(3))N-X-N=CH-(2-O,5-R-C(6)H(3))] (M = Ni (4), Cu (5), X = o-C(6)H(4), R = H; M = Ni (9), X = CH(2)CH(2), R = OH), and their corresponding ionic trinuclear [M{Fc-C(O)CH=C(CH(3))N-X-N=CH-(eta(6)-2-O,5-R-C(6)H(3))RuCp*}][PF(6)] (6, 7, 10), M[ONNO]-type unsymmetrical Salophen and salen complexes featuring ferrocenyl (Fc) donor and the mixed sandwich acceptor [Cp*Ru(eta(6)- salicylidene)](+) as a push-pull moiety are reported in this paper (Fc = CpFe(eta(5)-C(5)H(4)); Cp = eta(5)-C(5)H(5); Cp* = eta(5)-C(5)Me(5)). The single-crystal X-ray structure of the bimetallic iron-nickel derivative 4 indicates a bowed structure of the unsymmetrical Schiff base skeleton. The Ni(II) ion is tetracoordinated in a square planar environment, with two nitrogen atoms and two oxygen atoms as donors.

Theoretical and electrochemical studies on organometallic symmetrical schiff base complexes of Zn(II), Cu(II), Ni(II) and Co(II).

The electronic communication between two redox centres through a Schiff base complex has been investigated in a series of ethylenediimine-bis(1-ferrocenyl-1,3-butanedionate) complexes of Zn(II) 1, Cu(II) 2, Ni(II) 3 and Co(II) 4. Cyclic voltammetry experiments of 1 and 2 exhibit a unique two-electron reversible oxidation wave, whereas in the case of 3 and 4 two and three one-electron oxidation processes are, respectively, observed. These results suggest some electronic interaction between the iron atoms of the ferrocenyl groups.

Iron-molybdenum charge-transfer hybrids containing organometallic and inorganic fragments bridged by aryldiazenido ligands in a mu-eta(6):eta(1) coordination mode: syntheses, characterization, X-ray structures, electrochemistry, and theoretical investigation.

Representative members of a new family of covalently bonded charge-transfer molecular hybrids, of general formula [(eta5-C5H5)Fe(mu,eta6:eta1-p-RC6H4NN)Mo(eta2-S2CNEt2)3] +PF6- (R: H, 5+PF6-; Me, 6+PF6-; MeO, 7+PF6-) and [(eta5-C5Me5)Fe(mu,eta6:eta1-C6H5NN)Mo(eta2-S2CNEt2)3]+PF6-, 8+PF6-, have been synthesized by reaction of the corresponding mixed-sandwich organometallic hydrazines [(eta5-C5H5)Fe(eta6-p-RC6H4NHNH2)]+PF6- (R: H, 1+PF6-; Me, 2+PF6-; MeO, 3+PF6-) and [(eta5-C5Me5)Fe(eta6-C6H5NHNH2)]+PF6-, 4+PF6-, with cis-dioxomolybdenum(VI) bis(diethyldithiocarbamato) complex, [MoO2(S2CNEt2)2], in the presence of sodium diethyldithiocarbamato trihydrate, NaSC(=S)NEt2.3H2O, in refluxing methanol. These iron-molybdenum complexes consist of organometallic and inorganic fragments linked each other through a pi-conjugated aryldiazenido bridge coordinated in eta6 and eta1 modes, respectively.