JBIC Journal of Biological Inorganic Chemistry最新文献

In order to obtain the inorganic efficient antibacterial agents, the means of ion doping and morphology construction in this research are used to enhance the antibacterial property of nano-MgO, which is according to the “oxidative damage mechanism” and “contact mechanism”. In this work, the nano-textured Sc₂O₃-MgO are synthesized by doping Sc³⁺ in nano-MgO lattice through calcining at 600 °C. When the Sc³⁺ content reaches 10%, the nanotextures on the powders surface are pretty clearly visible and uniform, and the specific surface area and the oxygen vacancy are ideal, so that the 10% Sc³⁺-doped powders (SM-10) has the excellent antibacterial property against E. coli and S. aureus (MBC = 0.03 mg/mL). The efficient antibacterial agents in this research have a better antibacterial effect than the 0% Sc³⁺-doped powders (SM-0, MBC = 0.20 mg/mL) and the commercial nano-MgO (CM, MBC = 0.40 mg/mL), which have application prospects in the field of antibacterial.

[FeFe]-hydrogenases are gas-processing metalloenzymes that catalyze H₂ oxidation and proton reduction (H₂ release) in microorganisms. Their high turnover frequencies and lack of electrical overpotential in the hydrogen conversion reaction has inspired generations of biologists, chemists, and physicists to explore the inner workings of [FeFe]-hydrogenase. Here, we revisit 25?years of scientific literature on [FeFe]-hydrogenase and propose a personal account on ‘must-read’ research papers and review article that will allow interested scientists to follow the recent discussions on catalytic mechanism, O₂ sensitivity, and the in vivo synthesis of the active site cofactor with its biologically uncommon ligands?carbon monoxide and cyanide. Focused on—but not restricted to—structural biology and molecular biophysics, we highlight future directions that may inspire young investigators to pursue a career in the exciting and competitive field of [FeFe]-hydrogenase research.

Graphical abstract

The lytic polysaccharide monooxygenases (LPMOs) comprise a super-family of copper enzymes that boost the depolymerisation of polysaccharides by oxidatively disrupting the glycosidic bonds connecting the sugar units. Industrial use of LPMOs for cellulose depolymerisation has already begun but is still far from reaching its full potential. One issue is that the LPMOs self-oxidise and thereby deactivate. The mechanism of this self-oxidation is unknown, but histidine residues coordinating to the copper atom are the most susceptible. An unusual methyl modification of the NE2 atom in one of the coordinating histidine residues has been proposed to have a protective role. Furthermore, substrate binding is also known to reduce oxidative damage. We here for the first time investigate the mechanism of histidine oxidation with combined quantum and molecular mechanical (QM/MM) calculations, with outset in intermediates previously shown to form from a reaction with peroxide and a reduced LPMO. We show that an intermediate with a [Cu–O]⁺ moiety is sufficiently potent to oxidise the nearest C–H bond on both histidine residues, but methylation of the NE2 atom of His-1 increases the reaction barrier of this reaction. The substrate further increases the activation barrier. We also investigate a [Cu–OH]²⁺ intermediate with a deprotonated tyrosine radical. This intermediate was previously proposed to have a protective role, and we also find it to have higher barriers than the corresponding a [Cu–O]⁺ intermediate.

Graphical abstract

Thiol dioxygenases are a subset of non-heme mononuclear iron oxygenases that catalyze the O₂-dependent oxidation of thiol-bearing substrates to yield sulfinic acid products. Cysteine dioxygenase (CDO) and 3-mercaptopropionic acid (3MPA) dioxygenase (MDO) are the most extensively characterized members of this enzyme family. As with many non-heme mononuclear iron oxidase/oxygenases, CDO and MDO exhibit an obligate-ordered addition of organic substrate before dioxygen. As this substrate-gated O₂-reactivity extends to the oxygen-surrogate, nitric oxide (NO), EPR spectroscopy has long been used to interrogate the [substrate:NO:enzyme] ternary complex. In principle, these studies can be extrapolated to provide information about transient iron-oxo intermediates produced during catalytic turnover with dioxygen. In this work, we demonstrate that cyanide mimics the native thiol-substrate in ordered-addition experiments with MDO cloned from Azotobacter vinelandii (AvMDO). Following treatment of the catalytically active Fe(II)-AvMDO with excess cyanide, addition of NO yields a low-spin (S = 1/2) (CN/NO)-Fe-complex. Continuous wave and pulsed X-band EPR characterization of this complex produced in wild-type and H157N variant AvMDO reveal multiple nuclear hyperfine features diagnostic of interactions within the first- and outer-coordination sphere of the enzymatic Fe-site. Spectroscopically validated computational models indicate simultaneous coordination of two cyanide ligands replaces the bidentate (thiol and carboxylate) coordination of 3MPA allowing for NO-binding at the catalytically relevant O₂-binding site. This promiscuous substrate-gated reactivity of AvMDO with NO provides an instructive counterpoint to the high substrate-specificity exhibited by mammalian CDO for l-cysteine.

Graphical abstract

Novel ruthenium(III) complexes of general formula Na[RuCl₂(L¹⁻³-N,O)₂] where L^(1–3) denote deprotonated Schiff bases (HL¹-HL³) derived from 5-substituted salicyladehyde and alkylamine (propyl- or butylamine) were prepared and characterized based on elemental analysis, mass spectra, infrared, electron spin/paramagnetic resonance (ESR/EPR) spectroscopy, and cyclovoltammetric study. Optimization of five isomers of complex C1 was done by DFT calculation. The interaction of C1–C3 complexes with DNA (Deoxyribonucleic acid) and BSA (Bovine serum albumin) was investigated by electron spectroscopy and fluorescence quenching. The cytotoxic activity of C1–C3 was investigated in a panel of four human cancer cell lines (K562, A549, EA.hy926, MDA-MB-231) and one human non-tumor cell line (MRC-5). Complexes displayed an apparent cytoselective profile, with IC₅₀ values in the low micromolar range from 1.6 ± 0.3 to 23.0 ± 0.1 µM. Cisplatin-resistant triple-negative breast cancer cells MDA-MB-231 displayed the highest sensitivity to complexes, with Ru(III) compound containing two chlorides and two deprotonated N-propyl-5-chloro-salicylidenimine (hereinafter C1) as the most potent (IC₅₀ = 1.6 µM), and approximately ten times more active than cisplatin (IC₅₀ = 21.9 µM). MDA-MB-231 cells treated for 24 h with C1 presented with apoptotic morphology, as seen by acridine orange/ethidium bromide staining, while 48 h of treatment induced DNA fragmentation, and necrotic changes in cells, as seen by flow cytometry analysis. Drug-accumulation study by inductively coupled plasma mass spectrometry (ICP-MS) demonstrated markedly higher intracellular accumulation of C1 compared with cisplatin.

Graphical abstract

Zinc finger proteins are abundant in the human proteome and are responsible for a variety of functions. The domains that constitute zinc finger proteins are compact spherical structures, each comprising approximately 30 amino acid residues, but they also have precise molecular factor functions: zinc binding and DNA recognition. Due to the biological importance of zinc finger proteins and their unique structural and functional properties, many artificial zinc finger proteins have been created and are expected to improve their functions and biological applications. In this study, we review previous studies on the redesign and application of artificial zinc finger proteins, focusing on the experimental results obtained by our research group. In addition, we systematically review various design strategies used to construct artificial zinc finger proteins and discuss in detail their potential biological applications, including gene editing. This review will provide relevant information to researchers involved or interested in the field of artificial zinc finger proteins as a potential new treatment for various diseases.

This study aims at the synthesis and initial biological evaluation of novel rhenium–tricarbonyl complexes of 3,3′,4′,5,7-pentahydroxyflavone (quercetin), 3,7,4΄-trihydroxyflavone (resokaempferol), 5,7-dihydroxyflavone (chrysin) and 4΄,5,7-trihydroxyflavonone (naringenin) as neuroprotective and anti-PrP agents. Resokaempferol was synthesized from 2,2΄,4-trihydroxychalcone by H₂O₂/NaOH. The rhenium–tricarbonyl complexes of the type fac-[Re(CO)₃(Fl)(sol)] were synthesized by reacting the precursor fac-[Re(CO)₃(sol)₃]⁺ with an equimolar amount of the flavonoids (Fl) quercetin, resokaempferol, chrysin and naringenin and the solvent (sol) was methanol or water. The respective Re–flavonoid complexes were purified by semi-preparative HPLC and characterized by spectroscopic methods. Furthermore, the structure of Re–chrysin was elucidated by X-ray crystallography. Initial screening of the neuroprotective properties of these compounds included the in vitro assessment of the antioxidant properties by the DPPH assay as well as the anti-lipid peroxidation of linoleic acid in the presence of AAPH and their ability to inhibit soybean lipoxygenase. From the above studies, it was concluded that the complexes’ properties are mainly correlated with the structural characteristics and the presence of the flavonoids. The flavonoids and their respective Re-complexes were also tested in vitro for their ability to inhibit the formation and aggregation of the amyloid-like abnormal prion protein, PrP^Sc, by employing the real-time quaking-induced conversion assay with recombinant PrP seeded with cerebrospinal fluid from patients with Creutzfeldt–Jakob disease. All the compounds blocked de novo abnormal PrP formation and aggregation.

Graphical abstract

The emergence and rapid spread of the mobile colistin resistance gene mcr-1 among bacterial species and hosts significantly challenge the efficacy of “last-line” antibiotic colistin. Previously, we reported silver nitrate and auranofin serve as colistin adjuvants for combating mcr-1-positive bacteria. Herein, we uncovered more gold-based drugs and nanoparticles, and found that they exhibited varying degree of synergisms with colistin on killing mcr-1-positive bacteria. However, pre-activation of the drugs by either glutathione or N-acetyl cysteine, thus releasing and accumulating gold ions, is perquisite for their abilities to substitute zinc cofactor from MCR-1 enzyme. X-ray crystallography and biophysical studies further supported the proposed mechanism. This study not only provides basis for combining gold-based drugs and colistin for combating mcr-1-positive bacterial infections, but also undoubtedly opens a new horizon for metabolism details of gold-based drugs in overcoming antimicrobial resistance.

Graphical abstract

Guanine-rich quadruplex DNA (G-quadruplex) is of interest both in cell biology and nanotechnology. Its biological functions necessitate a G-quadruplex to be stabilized against escape of the monovalent metal cations. The potassium ion (({{varvec{K}}}^{+})) is particularly important as it experiences a potential energy barrier while it enters and exits the G-quadruplex systems which are normally found in human telomere. In the present work, we analyzed the time it takes for the ({{varvec{K}}}^{+}) cations to get in and out of the G-quadruplex. Our time estimate is based on entropic tunneling time—a time formula which gave biologically relevant results for DNA point mutation by proton tunneling. The potential energy barrier experienced by ({{varvec{K}}}^{+}) ions is determined from a quantum mechanical simulation study, Schrodinger equation is solved using MATLAB, and the computed eigenfunctions and eigenenergies are used in the entropic tunneling time formula to compute the time delay and charge accumulation rate during the tunneling of ({{varvec{K}}}^{+}) in G-quadruplex. The computations have shown that ion tunneling takes picosecond times. In addition, average ({{varvec{K}}}^{+}) accumulation rate is found to be in the picoampere range. Our results show that time delay during the ({{varvec{K}}}^{+}) ion tunneling is in the ballpark of the conformational transition times in biological systems, and it could be an important parameter for understanding its biological role in human DNA as well as for the possible applications in biotechnology. To our knowledge, for the first time in the literature, time delay during the ion tunneling from and into G-quadruplexes is computed.

Graphical abstract