Binding Of Zn Ions Research Articles

Identification of micronutrient deficiency related miRNA and their targets in Triticum aestivum using bioinformatics approach

Identification of miRNAs and their target proteins infer their functions to understand the biological processes of miRNAs and their involvement in plant growth and development. The homology-based approach (BLAST suite) was used for the identification of miRNA related to Zn and Cu deficiency in the bread wheat genome. Calculated the coding potential for the precursor miRNA and then predicted their secondary structure through RNAfold. PmiREN online server identified the miRNA target wheat protein. Further, STRING database predicted the biological relevance of the target protein. This in-silico study has identified the 3 miRNAs of the respective family of miR528, miR397, and miR168 of Triticum aestivum related to Cu and Zn deficiency. Out of the 42 targets for tae-miR397c; one of the targets is MFS domain-containing protein that contributes to “electron transfer” between photosystem700 and the “cytochrome b6-f complex” in photosystem and rest of the targets are laccase protein; involved in cell wall ligning deposition. Tae-miR528c has 6 targets; four are uncategorized proteins and the remaining two targets viz. GRF-type domain-containing protein and phytocyanin domain-containing protein are responsible for Zn ion binding and participate in electron transfer activity. The protein-protein interactions (PPIs) have found the various proteins that are associated with these identified miRNAs (tae-miR397c and tae-miR528c) target the protein that could be annotated further for their role in plant growth and development. The current computational hypothesis has developed a fast and robust pipeline to identify plant miRNAs and their targets compared to other used approaches.

Stabilizing Zn Metal Anode Through Regulation of Zn Ion Transfer and Interfacial Behavior with a Fast Ion Conductor Protective Layer.

Aqueous Zn-ion batteries (AZIBs) attract intensive attention owing to their environmental friendliness, cost-effectiveness, innate safety, and high specific capacity. However, the practical applications of AZIBs are hindered by several adverse phenomena, including corrosion, Zn dendrites, and hydrogen evolution. Herein, a Zn anode decorated with a 3D porous-structured Na3 V2 (PO4)3 (NVP@Zn) is obtained, where the NVP reconstruct the electrolyte/anode interface. The resulting NVP@Zn anode can provide a large quantity of fast and stable channels, facilitating enhanced Zn ion deposition kinetics and regulating the Zn ions transport process through the ion confinement effect. The NASICON-type NVP protective layer promote the desolvation process due to its nanopore structure, thus effectively avoiding side reactions. Theoretical calculations indicate that the NVP@Zn electrode has a higher Zn ion binding energy and a higher migration barrier, which demonstrates that NVP protective layer can enhance Zn ion deposition kinetics and prevent the unfettered 2D diffusion of Zn ions. Therefore, the results show that NVP@Zn/MnO2 full cell can maintain a high specific discharge capacity of 168mAhg-1 and a high-capacity retention rate of 74.6% after cycling. The extraordinary results obtained with this strategy have confirmed the promising applications of NVP in high-performance AZIBs.

ECEL1 novel mutation in arthrogryposis type 5D: A molecular dynamic simulation study.

ECEL1 has been presented as a causal gene of an autosomal recessive form distal arthrogryposis (DA) which affects the distal joints. The present study focused on bioinformatic analysis of a novel mutation in ECEL1, c.535A>G (p. Lys179Glu), which was reported in a family with 2 affected boys and fetus through prenatal diagnosis. Whole-exome sequencing data analyzed followed by molecular dynamic (MD) simulation of native ECEL1 protein and mutant structures using GROMACS software. One variant c.535A>G, p. Lys179Glu (homozygous) on gene ECEL1 has been detected in proband which was validated in all family members through Sanger sequencing. We demonstrated remarkable constructional differences by MD simulation between wild-type and novel mutant of ECEL1 gene. The reason for the lack of the Zn ion binding in mutation in the ECEL1 protein has been identified by average atomic distance and SMD analysis among the wild-type and mutant. Overall, in this study, we present knowledge of the effect of the studied variant on the ECEL1 protein leading to neurodegenerative disorder in humans. This work may hopefully be supplementary to classical molecular dynamics to dissolve the mutational effects of cofactor-dependent protein.

Bioinformatics and Molecular Insights to Anti-Metastasis Activity of Triethylene Glycol Derivatives.

The anti-metastatic and anti-angiogenic activities of triethylene glycol derivatives have been reported. In this study, we investigated their molecular mechanism(s) using bioinformatics and experimental tools. By molecular dynamics analysis, we found that (i) triethylene glycol dimethacrylate (TD-10) and tetraethylene glycol dimethacrylate (TD-11) can act as inhibitors of the catalytic domain of matrix metalloproteinases (MMP-2, MMP-7 and MMP-9) by binding to the S1’ pocket of MMP-2 and MMP-9 and the catalytic Zn ion binding site of MMP-7, and that (ii) TD-11 can cause local disruption of the secondary structure of vascular endothelial growth factor A (VEGFA) dimer and exhibit stable interaction at the binding interface of VEGFA receptor R1 complex. Cell-culture-based in vitro experiments showed anti-metastatic phenotypes as seen in migration and invasion assays in cancer cells by both TD-10 and TD-11. Underlying biochemical evidence revealed downregulation of VEGF and MMPs at the protein level; MMP-9 was also downregulated at the transcriptional level. By molecular analyses, we demonstrate that TD-10 and TD-11 target stress chaperone mortalin at the transcription and translational level, yielding decreased expression of vimentin, fibronectin and hnRNP-K, and increase in extracellular matrix (ECM) proteins (collagen IV and E-cadherin) endorsing reversal of epithelial–mesenchymal transition (EMT) signaling.

Changes Due to Ageing in the Glycan Structure of Alpha-2-Macroglobulin and Its Reactivity with Ligands.

Alpha-2-macroglobulin (α2M) is a molecule generally associated with inflammation, and chronic inflammation is associated with ageing and cancer. The degree of inflammation was recently proposed to be considered as a biomarker of biological ageing. In this study, glycans attached to α2M were analysed in a human population of different ages by lectin-based protein microarray. Higher reactivity of α2M with several lectins was detected in older individuals indicating an increased content of specific monosaccharides: α2,6 sialic acid, mannose and N-acetylglucosamine, and multiantennary complex type N-glycans. The increased glycosylation of α2M was accompanied by reduced binding of Zn ions and insulin-like growth factor-binding protein 2 (IGFBP-2). Glycosylation of α2M and its reactivity with IGFBP-2 is similarly affected by ageing and incidence of colon cancer, but the reactivity of α2M with Zn ions is differently affected, as the binding of Zn ions remains unaltered in patients with colon cancer compared to healthy middle-aged individuals. Thus, the binding of IGFBP-2 to α2M seems to be related to structural changes in the glycan moieties of α2M, whereas binding of Zn ions, most likely, is not.

Deciphering the loss of metal binding due to mutation D83G of human SOD1 protein causing FALS disease

Mutations in Cu/Zn superoxide dismutase 1 (SOD1) protein are found to be the causative factor, behind the majority of familial amyotrophic later sclerosis (FALS) cases. The mutations particularly on the metal (Zn) binding residues are found to increase the disease onset in the individuals suffering from FALS, while the presence of the metal ion (Zn) is essential for the catalytic activity and retaining the protein stability. Thus in our study, we focused on one such metal binding mutant (D83G) and assessed the impact of the mutation on protein structure and function. The influence of mutation was examined dynamically, using discrete molecular dynamics on both the native and mutant SOD1 protein respectively. Accordingly, the variation in conformational stability, residual flexibility and protein compactness along with the change in conformational free energy were monitored over the entire dynamic period. Moreover, the motion of native and mutant SOD1 was also observed via the essential dynamics. Besides, the disparity in Zn ion binding was inspected through distance analysis and steered molecular dynamics, correspondingly. Therefore, the study provides a better understanding over the profound effect of mutation on SOD1, both structurally and functionally, using computational approaches.

Zn-complex of a natural yellow chlorophyll catabolite

“Non-fluorescent” chlorophyll catabolites (NCCs) were named “rusty pigments” originally, as they easily oxidized to yellow chlorophyll catabolites (YCCs) and other colored natural “phyllobilins.” In the present work, binding of Zn(II)-ions by YCC and its methyl ester YCC-Me, and structural investigations of the resulting Zn(II)-complexes are reported. Binding of Zn-ions to the weakly luminescent YCC or YCC-Me in DMSO produces orange-yellow complexes that exhibit strong green emission. The Zn-complex of YCC-Me was isolated and characterized by UV-vis-, fluorescence-, mass- and NMR-spectra. The data revealed a 2:1 complex, Zn(YCC-Me)[Formula: see text], in which YCC-Me serves as bidentate ligand. The Zn(II)-center in Zn(YCC-Me)[Formula: see text] is, thereby, deduced to be coordinated in a pseudo tetrahedral fashion. Formation of Zn(YCC-Me)[Formula: see text] (and of Zn(YCC)[Formula: see text] is compatible with an isomerization of the lactam form of ring D to the corresponding lactim tautomer in these neutral Zn(II)-complexes.

Inhibition of SARS Coronavirus Helicase by Baicalein

The severe acute respiratory syndrome (SARS) occurred in the southern part of China in the late 2002 and rapidly spread to Canada and Southeast Asian countries, including Singapore, Vietnam, Hong Kong, and Taiwan. During the outbreak, clinicians were unaware of which treatments were appropriate to treat SARS patients because they had no prior experience in dealing with this disease. Therefore, they prescribed the SARS patients with general antiviral medications, such as ribavirin, type-I interferon and corticosteroids. The SARS pandemic was finally controlled within a year of outbreak through progressive global efforts, including patient quarantine. A retrospective case-controlled analysis showed that these antiviral agents had minimal beneficial effects or even worsened the symptoms of SARS patients, suggesting that it is necessary to develop effective anti-SARS agents for another SARS outbreak in the future. A novel coronavirus (CoV) was identified as a causal factor for the SARS. Coronaviruses are members of a family of enveloped viruses that replicate in the cytoplasm of host cells. Analysis of the full sequence of the SARS coronavirus (SCV) revealed that it is a large, single-stranded, and positive-sense RNA virus, which bears a moderate resemblance with other human coronaviruses, HCoV-OC43 and HCoV229E. Notably, the first 2/3 of the SCV genome consists of the viral replicase genes that encode 16 non-structural proteins (nsPs), including the NTPase/helicase (nsP13). The SCV helicase, nsP13 is a critical component for viral replication and currently regarded as a feasible drug target for potential SCV chemical inhibitors. Helicase is a molecular motor protein that separates double-stranded nucleic acid (NA), using the free energy generated from nucleoside triphosphate (NTP) hydrolysis during translocation on singlestranded NA. The nsP13 is considered as a RNA helicase because SCV is a positive-strand ssRNA virus and comprise three major domains: Zn ion binding domain, hinge domain and NTPase/helicase domain. Previous studies have identified numerous natural or synthetic chemicals that suppress the nsP13 activity with different modes of actions. For example, Tanner et al. have demonstrated that the bananin derivatives are non-competitive inhibitors of the ATPase activity of nsP13. Yang et al. have demonstrated that bismuth complexes compete for the Zn ion binding sites, thereby exhibiting significant inhibitory effects on both the ATPase and DNA duplex-unwinding activities of nsP13. Lee et al. have found that aryl diketoacid (ADK) analogs suppress the nsP13 activity. Because ADKs are well-known metal chelators, authors initially speculated that ADKs would inhibit the activity of nsP13 in an analogous manner to the bismuth complexes: ADKs bind to Zn ion binding site, thereby inhibiting both the ATPase and DNA duplex-unwinding activities. Contrary to their expectations, however, they observed that ADKs selectively inhibited the duplex DNA-unwinding activity, but not the ATPase activity of nsP13 and the anti-SCV helicase activities of ADKs were dependent on regiochemistry as well as the substituent of ADKs, leading to the conclusion that alternative inhibitory mechanism(s) of the nsP13 activity by ADKs might exist. In accordance with the above observations, we have recently conducted in vitro biochemical experiments to find out dietary or medicinal compounds that possess significant inhibitory effects on the nsP13 helicase activity. As a result, we found that both myricetin and scutellarein (Fig. 1) strongly inhibited the ATPase activity, but not the DNA unwinding activity of nsP13. IC50 values of myricetin and scutellarein against the ATPase activity of nsP13 were observed to be 2.71 ± 0.19 μM and 0.86 ± 0.48 μM, respectively. It is notable that myricetin and scutellarein are natural flavonoids. Flavonoids are secondary plant metabolites that

Impact of normal or low organic mineral (Cu, Zn, Mn) diets on gene expression patterns in the intestine of broiler chicks

We assessed the impact of early life mineral (Zn, Cu, Mn) nutrition on gene expression in the jejunum. Broiler chicks were randomly assigned to 1 of 3 treatments. Corn‐soy diets had organic Zn, Cu, and Mn (BioPlex®, Alltech Inc.) at 100% (normal, N) or 20% (low, L) of NRC requirements. Diets were fed for 5 d, followed by a second diet (d 6–21), creating 3 groups: N‐N, N‐L, or L‐L. On d 21, birds were euthanized and gene expression was analyzed using the Affymetrix Chicken Genome Array. Compared to N‐N, the number of genes significantly changed was 303 for N‐L and 530 for L‐L, with 154 commonly affected. Both N‐L and L‐L led to down‐regulation of genes metallothionein 3 and 4 compared to N‐N. Gene ontology (GO) classifications showed that L‐L had a greater impact than N‐L on genes associated with metal ion transport, Zn ion binding and carbohydrate metabolic processes. IPA analysis showed the top biologic functions affected by N‐L were cell signaling, cellular function and maintenance, and cell morphology; for L‐L they were protein synthesis, cell death and post‐translational modification. Although both groups were fed the same diet d 6 – 21, IL‐17A pathways were enriched with L‐L only. Thus, mineral levels up to 5 d of life altered gene expression in birds on d 21, suggesting that early nutrition has a significant, long term impact on gene response in the intestine of young chickens.

Homology modelling and active-site-mutagenesis study of the catalytic domain of the pneumococcal phosphorylcholine esterase

Streptococcus pneumoniae is among the major human pathogens. Several interactions of this bacterium with its host appear to have been mediated by bacterial cell wall components. Specifically, phosphorylcholine residues covalently attached to teichoic and lipoteichoic acids serve as anchors for many surface-located proteins (choline-binding proteins CBPs), including cell-adhesion and virulence factors, and are also recognized by host response components through choline-binding receptors. In this study, we have performed modelling of the catalytic domain of pneumococcal phosphorylcholine esterase (Pce), a modular enzyme that is capable of removing phosphorycholine residues from teichoic and lipoteichoic acids, remodelling their distribution on the bacterial envelope. We wish to contribute to the structural knowledge of Pce. In this pursuit, 3D models of Pce have been established by homology modelling, using the X-ray structure of enzymes from the α/β metallo-lactamase family fold as templates. Theoretical models of pneumococcal phosphorylcholine esterase (Pce) catalytic modules obtained by homology modelling, and corresponding docking studies employed to find out the residues involved in the binding of Zn ions, are discussed according to mutational studies and ab initio calculations. The presence of a binuclear Zn cluster in the catalytic domain of Pce and a likely coordination model are proposed.

Dinucleotide Hydrolysis Promoted by Dinuclear Zn Complexes − The Effect of the Distance between Zn Ions in the Complexes on the Hydrolysis Rate

The rate of hydrolysis of an RNA dimer, uridylyl(3′→5′)uridine (UpU), promoted by dinuclear Zn complexes resulting from a series of ligands with differently spaced Zn ion binding sites, was examined. Although the ligands in the present study have in common two di-2-pyridylmethylamino moieties as the Zn binding sites, the activities of these ligands toward the hydrolysis were quite different. Our results suggest that the distance between metal ion coordination sites is an essential factor for the intrinsic activities of the dinuclear complexes.

Activation of pyridoxal kinase by metallothionein

Brain pyridoxal kinase, which uses ATP complexed to either Zn(II) or Co(II) as substrates, displays high catalytic activity in the presence of Zn-thionein and Co-thionein. Several steps intervene in the process of pyridoxal kinase activation, i.e., binding of Zn ions to ATP and interaction between Zn-ATP and the enzyme. Equilibrium binding studies show that ATP mediates the release of Zn ions from the metal-thiolate clusters of the thioneins, whereas spectroscopic measurements conducted on Co-thionein reveal that the absorption transitions corresponding to the metal-thiolate of the protein are perturbed by ATP. The binding Zn-ATP to the kinase proceeds with a ΔG = − 6.3 kcal/mol as demonstrated by fluorometric titrations. Direct interaction between the kinase and derivatized-metallothionein could not be detected by emission anisotropy measurements, indicating that juxtaposition of the proteins does not influence the exchange of metal ions. Since the concentration of free Zn in several mammalian tissues is lower than 1 nM, it is postulated that under in vivo conditions the concentration of metallothionein regulates the catalytic activity of pyridoxal kinase.