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INTS11 and CPSF73 are metal-dependent endonucleases for Integrator and pre-mRNA 3'-end processing, respectively. Here, we show that the INTS11 binding partner BRAT1/CG7044, a factor important for neuronal fitness, stabilizes INTS11 in the cytoplasm and is required for Integrator function in the nucleus. Loss of BRAT1 in neural organoids leads to transcriptomic disruption and precocious expression of neurogenesis-driving transcription factors. The structures of the human INTS9-INTS11-BRAT1 and Drosophila dIntS11-CG7044 complexes reveal that the conserved C terminus of BRAT1/CG7044 is captured in the active site of INTS11, with a cysteine residue directly coordinating the metal ions. Inspired by these observations, we find that UBE3D is a binding partner for CPSF73, and UBE3D likely also uses a conserved cysteine residue to directly coordinate the active site metal ions. Our studies have revealed binding partners for INTS11 and CPSF73 that behave like cytoplasmic chaperones with a conserved impact on the nuclear functions of these enzymes.
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Núcleo Celular , Citoplasma , Proteínas de Drosophila , Ligação Proteica , Humanos , Animais , Núcleo Celular/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Citoplasma/metabolismo , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Endonucleases/metabolismo , Endonucleases/genética , Células HEK293 , Neurogênese/genética , Fator de Especificidade de Clivagem e Poliadenilação/metabolismo , Fator de Especificidade de Clivagem e Poliadenilação/genética , Domínio CatalíticoRESUMO
U7 snRNP is a multisubunit endonuclease required for 3' end processing of metazoan replication-dependent histone pre-mRNAs. In contrast to the spliceosomal snRNPs, U7 snRNP lacks the Sm subunits D1 and D2 and instead contains two related proteins, Lsm10 and Lsm11. The remaining five subunits of the U7 heptameric Sm ring, SmE, F, G, B, and D3, are shared with the spliceosomal snRNPs. The pathway that assembles the unique ring of U7 snRNP is unknown. Here, we show that a heterodimer of Lsm10 and Lsm11 tightly interacts with the methylosome, a complex of the arginine methyltransferase PRMT5, MEP50, and pICln known to methylate arginines in the carboxy-terminal regions of the Sm proteins B, D1, and D3 during the spliceosomal Sm ring assembly. Both biochemical and cryo-EM structural studies demonstrate that the interaction is mediated by PRMT5, which binds and methylates two arginine residues in the amino-terminal region of Lsm11. Surprisingly, PRMT5 also methylates an amino-terminal arginine in SmE, a subunit that does not undergo this type of modification during the biogenesis of the spliceosomal snRNPs. An intriguing possibility is that the unique methylation pattern of Lsm11 and SmE plays a vital role in the assembly of the U7 snRNP.
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Ribonucleoproteína Nuclear Pequena U7 , Ribonucleoproteínas Nucleares Pequenas , Animais , Ribonucleoproteína Nuclear Pequena U7/química , Metilação , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Histonas/metabolismo , Arginina/químicaRESUMO
Human cleavage and polyadenylation specificity factor (CPSF)73 (also known as CPSF3) is the endoribonuclease that catalyzes the cleavage reaction for the 3'-end processing of pre-mRNAs. The active site of CPSF73 is located at the interface between a metallo-ß-lactamase domain and a ß-CASP domain. Two metal ions are coordinated by conserved residues, five His and two Asp, in the active site, and they are critical for the nuclease reaction. The metal ions have long been thought to be zinc ions, but their exact identity has not been examined. Here we present evidence from inductively coupled plasma mass spectrometry and X-ray diffraction analyses that a mixture of metal ions, including Fe, Zn, and Mn, is present in the active site of CPSF73. The abundance of the various metal ions is different in samples prepared from different expression hosts. Zinc is present at less than 20% abundance in a sample expressed in insect cells, but the sample is active in cleaving a pre-mRNA substrate in a reconstituted canonical 3'-end processing machinery. Zinc is present at 75% abundance in a sample expressed in human cells, which has comparable endonuclease activity. We also observe a mixture of metal ions in the active site of the CPSF73 homolog INTS11, the endonuclease for Integrator. Taken together, our results provide further insights into the role of metal ions in the activity of CPSF73 and INTS11 for RNA 3'-end processing.
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Fator de Especificidade de Clivagem e Poliadenilação , Endonucleases , Humanos , Domínio Catalítico , Fator de Especificidade de Clivagem e Poliadenilação/química , Fator de Especificidade de Clivagem e Poliadenilação/metabolismo , Endonucleases/química , Endonucleases/metabolismo , Processamento Pós-Transcricional do RNA , Zinco/metabolismoRESUMO
ReS2 and ReSe2 have recently been enthusiastically studied owing to the specific in-plane electrical, optical and structural anisotropy caused by their distorted one-layer trigonal (1 T) phase, whereas other traditional transition-metal dichalcogenides (TMDCs, e.g. MoS2 and WSe2) have a hexagonal structure. Because of this special property, more and versatile nano-electronics and nano-optoelectronics devices can be developed. In this work, 2D materials in the series ReS2-x Se x (0 ≤ x ≤ 2) have been successfully grown by the method of chemical vapor transport. The direct and indirect resonant emissions of the complete series of layers can be simultaneously detected by polarized micro-photoluminescence (µPL) spectroscopy when the thickness of the ReS2-x Se x is greater than â¼70 nm. When it is less than 70 nm, only three direct excitonic emissions-E 1ex, E 2ex and E Sex-are detected. For the thick (bulk) ReS2-x Se x , more stacking of the ReX2 monolayers even flattens and shifts the valence-band maximum from Γ to the other K- or M-related points, thus leading to the coexistence of direct and indirect resonant light emissions from the c-plane ReX2. The transmittance absorption edge of each bulk ReX2 (a few microns thick) usually has a lower energy than those of the direct E 1ex and E 2ex excitonic emissions to form indirect absorption. The coexistence of direct and indirect emissions in ReX2 is a unique characteristic of a 2D layered semiconductor possessing triclinic low symmetry.
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BACKGROUNDS: A new highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi Arabia and quickly spread to some European countries since September 2012. Until 15 May 2014, it has infected at least 572 people with a fatality rate of about 30% globally. Studies to understand the virus and to develop antiviral drugs or therapy are necessary and urgent. In the present study, MERS-CoV papain-like protease (PLpro) is expressed, and its structural and functional consequences are elucidated. RESULTS: Circular dichroism and Tyr/Trp fluorescence analyses indicated that the secondary and tertiary structure of MERS-CoV PLpro is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PLpro is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PLpro exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PLpro. A natural mutation, Leu105, is the major reason for this difference. CONCLUSIONS: Overall, MERS-CoV PLpro bound by an endogenous metal ion shows a folded structure and potent proteolytic and deubiquitination activity. These findings provide important insights into the structural and functional properties of coronaviral PLpro family, which is applicable to develop strategies inhibiting PLpro against highly pathogenic coronaviruses.
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Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Proteínas Virais/química , Proteínas Virais/genética , Antivirais/química , Proteases 3C de Coronavírus , Cisteína Endopeptidases/biossíntese , Europa (Continente) , Regulação Viral da Expressão Gênica , Humanos , Íons/química , Metais/química , Processamento de Proteína Pós-Traducional , Proteólise , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/química , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/enzimologia , Proteínas Virais/biossínteseRESUMO
Pseudomonas aeruginosa is an opportunistic pathogen that thrives in environments associated with human activity, including soil and water altered by agriculture or pollution. Because L-lactate is a significant product of plant and animal metabolism, it can serve as a carbon source for P. aeruginosa in the diverse settings that it inhabits. In this study, we evaluate the production and use of two redundant P. aeruginosa L-lactate dehydrogenases, termed LldD and LldA. We confirm that the protein LldR represses lldD and identify a new transcription factor, called LldS, that activates lldA; these distinct regulators and the genomic contexts of lldD and lldA contribute to their differential expression. We demonstrate that the lldD and lldA genes are conditionally controlled in response to lactate isomers as well as to glycolate and É-hydroxybutyrate, which, like lactate, are É-hydroxycarboxylates. We also show that lldA is induced when iron availability is low. Our examination of lldD and lldA expression across depth in biofilms indicates a complex pattern that is consistent with the effects of glycolate production, iron availability, and cross-regulation on enzyme preference. Finally, macrophage infection assays reveal that both lldD and lldA contribute to persistence within host cells, underscoring the potential role of L-lactate as a carbon source during P. aeruginosa-eukaryote interactions. Together, these findings help us understand the metabolism of a key resource that may promote P. aeruginosa's success as a resident of contaminated environments and animal hosts.IMPORTANCEPseudomonas aeruginosa is a major cause of lung infections in people with cystic fibrosis, of hospital-acquired infections, and of wound infections. It consumes L-lactate, which is found at substantial levels in human blood and tissues. In this study, we investigated the spatial regulation of two redundant enzymes, called LldD and LldA, which enable L-lactate metabolism in P. aeruginosa biofilms. We uncovered mechanisms and identified compounds that control the preference of P. aeruginosa for LldD versus LldA. We also showed that both enzymes contribute to its ability to survive within macrophages, a behavior that is thought to augment the chronicity and recalcitrance of infections. Our findings shed light on a key metabolic strategy used by P. aeruginosa and have the potential to inform the development of therapies targeting bacterial metabolism during infection.
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Pseudomonas aeruginosa is an opportunistic pathogen that thrives in environments associated with human activity, including soil and water altered by agriculture or pollution. Because L-lactate is a significant product of plant and animal metabolism, it is available to serve as a carbon source for P. aeruginosa in the diverse settings it inhabits. Here, we evaluate P. aeruginosa's production and use of its redundant L-lactate dehydrogenases, termed LldD and LldA. We confirm that the protein LldR represses lldD and identify a new transcription factor, called LldS, that activates lldA; these distinct regulators and the genomic contexts of lldD and lldA contribute to their differential expression. We demonstrate that the lldD and lldA genes are conditionally controlled in response to lactate isomers as well as to glycolate and - hydroxybutyrate, which, like lactate, are -hydroxycarboxylates. We also show that lldA is induced when iron availability is low. Our examination of lldD and lldA expression across depth in biofilms indicates a complex pattern that is consistent with the effects of glycolate production, iron availability, and cross-regulation on enzyme preference. Finally, macrophage infection assays revealed that both lldD and lldA contribute to persistence within host cells, underscoring the potential role of L-lactate as a carbon source during P. aeruginosa-eukaryote interactions. Together, these findings help us understand the metabolism of a key resource that may promote P. aeruginosa's success as a resident of contaminated environments and animal hosts.
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The adaptation of egg-derived H7N9 candidate vaccine virus (CVV) in the mammalian cell line is an approach to developing a high-growth virus strain for the mass production of vaccine manufacturing. The adaptive mutations that occur in hemagglutinin (HA) are critical to the activity and potency of the vaccine virus. Previously, we identified a new mutation of A169S in the HA protein of an MDCK-adapted H7N9 vaccine virus (A/Anhui/2013, RG268); however, whether and how this mutation affects vaccine potency remain to be investigated. In this study, we serially passaged RG268 in MDCK cells and found that the HA titer and the TCID50 of the passaged virus RG268-M5 were 4-fold (HA units/50 µL) and 3.5-fold (log10 TCID50/mL) higher than those of the original CVV. By inspecting tandem MS spectra, we identified a new glycosylation site at N167 near the receptor binding site of the HA protein of RG268-M5. Flow cytometry results revealed that RG268-M5 could efficiently infect MDCK cells and initiate viral protein replication as well as that of RG268. Though the new glycosylation site is in the antigenic epitope of viral HA protein, the HI assay result indicated that the antigenicity of RG268-M5 was similar to RG268. Additionally, immunizing mice with RG268-M5 mixed aluminum hydroxide could induce potent antibody responses against the homologous and heterologous H7N9 viruses in vitro whereas the titers were comparable with those from the RG268 group. These results provide in-depth structural information regarding the effects of site-specific glycosylation on virus properties, which have implications for novel avian influenza vaccine development.
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U7 snRNP is a multi-subunit endonuclease required for 3' end processing of metazoan replication-dependent histone pre-mRNAs. In contrast to the spliceosomal snRNPs, U7 snRNP lacks the Sm subunits D1 and D2 and instead contains two related proteins, Lsm10 and Lsm11. The remaining five subunits of the U7 heptameric Sm ring, SmE, F, G, B and D3, are shared with the spliceosomal snRNPs. The pathway that assembles the unique ring of U7 snRNP is unknown. Here, we show that a heterodimer of Lsm10 and Lsm11 tightly interacts with the methylosome, a complex of the arginine methyltransferase PRMT5, MEP50 and pICln known to methylate arginines in the C-terminal regions of the Sm proteins B, D1 and D3 during the spliceosomal Sm ring assembly. Both biochemical and Cryo-EM structural studies demonstrate that the interaction is mediated by PRMT5, which binds and methylates two arginine residues in the N-terminal region of Lsm11. Surprisingly, PRMT5 also methylates an N-terminal arginine in SmE, a subunit that does not undergo this type of modification during the biogenesis of the spliceosomal snRNPs. An intriguing possibility is that the unique methylation pattern of Lsm11 and SmE plays a vital role in the assembly of the U7 snRNP.
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Integrator is a multi-subunit protein complex associated with RNA polymerase II (Pol II), with critical roles in noncoding RNA 3'-end processing and transcription attenuation of a broad collection of mRNAs. IntS11 is the endonuclease for RNA cleavage, as a part of the IntS4-IntS9-IntS11 Integrator cleavage module (ICM). Here we report a cryo-EM structure of the Drosophila ICM, at 2.74 Å resolution, revealing stable association of an inositol hexakisphosphate (IP6) molecule. The IP6 binding site is located in a highly electropositive pocket at an interface among all three subunits of ICM, 55 Å away from the IntS11 active site and generally conserved in other ICMs. We also confirmed IP6 association with the same site in human ICM. IP6 binding is not detected in ICM samples harboring mutations in this binding site. Such mutations or disruption of IP6 biosynthesis significantly reduced Integrator function in snRNA 3'-end processing and mRNA transcription attenuation. Our structural and functional studies reveal that IP6 is required for Integrator function in Drosophila, humans, and likely other organisms.
Assuntos
Ácido Fítico , RNA Polimerase II , Animais , Drosophila/metabolismo , Endonucleases , Humanos , Ácido Fítico/metabolismo , RNA Polimerase II/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Nuclear Pequeno/metabolismo , RNA não TraduzidoRESUMO
Three-finger toxins (3FTXs) are the most clinically relevant components in cobra (genus Naja) venoms. Administration of the antivenom is the recommended treatment for the snakebite envenomings, while the efficacy to cross-neutralize the different cobra species is typically limited, which is presumably due to intra-specific variation of the 3FTXs composition in cobra venoms. Targeting the clinically relevant venom components has been considered as an important factor for novel antivenom design. Here, we used the recombinant type of long-chain α-neurotoxins (P01391), short-chain α-neurotoxins (P60770), and cardiotoxin A3 (P60301) to generate a new immunogen formulation and investigated the potency of the resulting antiserum against the venom lethality of three medially important cobras in Asia, including the Thai monocled cobra (Naja kaouthia), the Taiwan cobra (Naja atra), and the Thai spitting cobra (Naja Siamensis) snake species. With the fusion of protein disulfide isomerase and the low-temperature settings, the correct disulfide bonds were built on these recombinant 3FTXs (r3FTXs), which were confirmed by the circular dichroism spectra and tandem mass spectrometry. Immunization with r3FTX was able to induce the specific antibody response to the native 3FTXs in cobra venoms. Furthermore, the horse and rabbit antiserum raised by the r3FTX mixture is able to neutralize the venom lethality of the selected three medically important cobras. Thus, the study demonstrated that the r3FTXs are potential immunogens in the development of novel antivenom with broad neutralization activity for the therapeutic treatment of victims involving cobra snakes in countries.
Assuntos
Antivenenos/administração & dosagem , Venenos Elapídicos/toxicidade , Neurotoxinas/toxicidade , Toxinas Três Dedos/administração & dosagem , Animais , Anticorpos Neutralizantes/sangue , Venenos Elapídicos/imunologia , Elapidae , Escherichia coli/genética , Cavalos , Imunização , Camundongos Endogâmicos ICR , Neurotoxinas/imunologia , Coelhos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química , Toxinas Três Dedos/química , Toxinas Três Dedos/genéticaRESUMO
We applied a thermal-desorption gas-chromatograph mass-spectrometer (TD-GC-MS) system to identify the marker volatile organic compounds (VOCs) in the aroma of red wine. After obtaining the marker VOC, we utilized surface acoustic waves (SAWs) to develop a highly sensitive sensing system as 'electronic nose' to detect these marker VOC. The SAW chips were fabricated on a LiNbO3 substrate with a lithographic process. We coated sensing polymers on the sensing area to adsorb the marker VOC in a sample gas. The adsorption of the marker VOC altered the velocity of the SAW according to a mass-loading effect, causing a frequency decrease. This experiment was conducted with wines of three grape varieties-cabernet sauvignon, merlot and black queen. According to the results of TD-GC-MS, the King brand of red wine is likely to have unique VOC, which are 2-pentanone, dimethyl disulfide, 2-methylpropyl acetate and 2-pentanol; Blue Nun-1 probably has a special VOC such as 2,3-butanedione. We hence used a SAW sensor array to detect the aroma of red wines and to distinguish their components by their frequency shift. The results show that the use of polyvinyl butyral (PVB) as a detecting material can distinguish Blue Nun-2 from the others and the use of polyvinyl alcohol (PVA) can distinguish King from the others. We conducted random tests to prove the accuracy and the reliability of our SAW sensors.
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The tumor necrosis factor receptor associated protein 1 (TRAP1) is a mitochondria chaperon protein that has been previously implicated as a target for cancer therapy due to its expression level is linked to tumor progression. In this study, an immunodominant phosphopeptide of TRAP1 was identified from an HLA-A2 gene transfected mouse cancer cell line using mass spectrometry, and a synthetic phosphopeptide was generated to evaluate the potency on cancer immunotherapy. In the transporter associated with antigen processing (TAP) deficient cell, the conjugated phosphate group plays a critical role to enhance the binding affinity of phosphopeptide with HLA-A2 molecule. On the basis of immunological assay, immunization of synthetic phosphopeptide could induce a high frequency of IFN-γ-secreting CD8+ T cells in HLA-A2 transgenic mice, and the stimulated cytotoxic T lymphocytes showed a high target specificity to lysis the epitope-pulsed splenocytes in vivo and the human lung cancer cell in vitro. In a tumor challenge assay, vaccination of the HLA-A2 restricted phosphopeptide appeared to suppress the tumor growth and prolong the survival period of tumor-bearing mice. These results suggest that novel phosphopeptide is naturally presented as a HLA-A2-restricted CTL epitope and capable of being a potential candidate for the development of therapeutic vaccine against high TRAP1-expressing cancers.
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Native disulfide formation is crucial to the process of disulfide-rich protein folding in vitro. As such, analysis of the disulfide bonds can be used to track the process of the folding reaction; however, the diverse structural isomers interfere with characterization due to the non-native disulfide linkages. Previously, a mass spectrometry (MS) based platform coupled with peptide demethylation and an automatic disulfide bond searching engine demonstrated the potential to screen disulfide-linked peptides for the unambiguous assignment of paired cysteine residues of toxin components in cobra venom. The developed MS-based platform was evaluated to analyze the disulfide bonds of structural isomers during the folding reaction of synthetic cardiotoxin A3 polypeptide (syn-CTX A3), an important medical component in cobra venom. Through application of this work flow, a total of 13 disulfide-linked peptides were repeatedly identified across the folding reaction, and two of them were found to contain cysteine pairings, like those found in native CTX A3. Quantitative analysis of these disulfide-linked peptides showed the occurrence of a progressive disulfide rearrangement that generates a native disulfide bond pattern on syn-CTX A3 folded protein. The formation of these syn-CTX A3 folded protein reaches a steady level in the late stage of the folding reaction. Biophysical and cell-based assays showed that the collected syn-CTX A3 folded protein have a ß-sheet secondary structure and cytotoxic activity similar to that of native CTX A3. In addition, the immunization of the syn-CTX A3 folded proteins could induce neutralization antibodies against the cytotoxic activity of native CTX A3. In contrast, these structure activities were poorly observed in the other folded isomers with non-native disulfide bonds. The study highlights the ability of the developed MS platform to assay isomers with heterogeneous disulfide bonds, providing insight into the folding mechanism of the bioactive protein generation.
Assuntos
Proteínas Cardiotóxicas de Elapídeos/química , Dissulfetos/química , Peptídeos/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Proteínas Cardiotóxicas de Elapídeos/farmacologia , Células HL-60 , Humanos , Isomerismo , Espectrometria de Massas , Naja naja , Peptídeos/farmacologia , Dobramento de Proteína , Estrutura Secundária de ProteínaRESUMO
Determining the precursor/product ion pair and optimal collision energy are the critical steps for developing a multiple reaction monitoring (MRM) assay using triple quadruple mass spectrometer for protein quantitation. In this study, a platform consisting of stable isotope dimethyl labeling coupled with triple-quadruple mass spectrometer was used to quantify the protein components of the influenza vaccines. Dimethyl labeling of both the peptide N-termini and the ϵ-amino group of lysine residues was achieved by reductive amination using formaldehyde and sodium cyanoborohydrate. Dimethylated peptides are known to exhibit dominant a1 ions under gas phase fragmentation in a mass spectrometer. These a1 ions can be predicted from the peptide N-terminal amino acids, and their signals do not vary significantly across a wide range of collision energies, which facilitates the determination of MRM transition settings for multiple protein targets. The intrinsic a1 ions provide sensitivity for acquiring MRM peaks that is superior to that of the typical b/y ions used for native peptides, and they also provided good linearity (R2â¯≥â¯0.99) at the detected concentration range for each peptide. These features allow for the simultaneous quantification of hemagglutinin and neuraminidase in vaccines derived from either embryo eggs or cell cultivation. Moreover, the low abundant ovalbumin residue originated from the manufacturing process can also be determined. The results demonstrate that the stable isotope dimethyl labeling coupled with MRM Mass spectrometry screening of a1 ions (i.e., SIDa-MS) can be used as a high-throughput platform for multiple protein quantification of vaccine products.
Assuntos
Antígenos Virais/análise , Vacinas contra Influenza/análise , Marcação por Isótopo/métodos , Espectrometria de Massas em Tandem/métodos , Antígenos Virais/química , Vacinas contra Influenza/química , Limite de Detecção , Modelos Lineares , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/química , Reprodutibilidade dos Testes , Proteínas Virais/análise , Proteínas Virais/químicaRESUMO
A wide gap semiconductor material has attracted attention as a heterophotocatalyst because of its light harvesting nature to be used in alternative energy production for the next generation. We, herein, grow and synthesize ZnS(1-x)O x series compounds using the chemical vapor transport (CVT) method with I2 serving as the transport agent. Different crystals, such as undoped ZnS and oxygen-doped ZnS0.94O0.06 and ZnS0.88O0.12, revealed different bright palette emissions that were presented in photoluminescence spectra in our previous report. To study the electron-hole pair interaction of this sample series, the near-band-edge transitions of the sample series were characterized in detail by photoconductivity (PC) experiments. Additional results from surface photovoltage (SPV) spectra also detected the surface and defect-edge transitions from the higher oxygen-doped ZnS crystals. PC measurement results showed a red-shift in the bandgap with increasing incorporation of oxygen on ZnS. Consequently, the samples were subjected to photoirradiation by xenon lamp for the degradation of methylene blue (MNB) by acting as heterophotocatalysts. Undoped ZnS emerged as the best photocatalyst candidate with the fastest rate constant value of 0.0277 min-1. In cubic {111} ZnS [{111} c-ZnS], the polarized Zn+ â S- ions may play a vital role as a photocatalyst because of their strong electron-hole polarization, which leads to the mechanism for degradation of the MNB solution.
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Flexible optoelectronics devices play an important role for technological applications of 2D materials because of their bendable, flexible and extended two-dimensional surfaces. In this work, light emission properties of layered gallium selenide (GaSe) crystals with different curvatures have been investigated using bending photoluminescence (BPL) experiments in the curvature range between R -1 = 0.00 m-1 (flat condition) and R -1 = 30.28 m-1. A bendable and rotated sample holder was designed to control the curvature (strain) of the layered sample under upward bending uniformly. The curvature-dependent BPL results clearly show that both bandgaps and BPL intensities of the GaSe are curvature dependent with respect to the bending-radius change. The main emission peak (bandgap) is 2.005 eV for flat GaSe, and is 1.986 eV for the bending GaSe with a curvature of 30.28 m-1 (the maximum bending conditions in this experiment). An obvious redshift (i.e. energy reduction) for the GaSe BPL peak was detected owing to the c-plane lattice expansion by upward bending. The intensities of the corresponding BPL peaks also show an increase with increasing curvature. The correlations between BPL peak intensity, shiny area and bond-angle widening of the bent GaSe under laser excitation have been discussed. The lattice constant versus emission energies of the bending GaSe was also analyzed. An estimated lattice constant vs. bandgap relation was present for further application of the layered GaSe in bendable flexible light-emission devices.
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Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in southern China in late 2002 and caused a global outbreak with a fatality rate around 10% in 2003. Ten years later, a second highly pathogenic human CoV, MERS-CoV, emerged in the Middle East and has spread to other countries in Europe, North Africa, North America and Asia. As of November 2017, MERS-CoV had infected at least 2102 people with a fatality rate of about 35% globally, and hence there is an urgent need to identify antiviral drugs that are active against MERS-CoV. Here we show that a clinically available alcohol-aversive drug, disulfiram, can inhibit the papain-like proteases (PLpros) of MERS-CoV and SARS-CoV. Our findings suggest that disulfiram acts as an allosteric inhibitor of MERS-CoV PLpro but as a competitive (or mixed) inhibitor of SARS-CoV PLpro. The phenomenon of slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicate covalent inactivation of SARS-CoV PLpro by disulfiram, while synergistic inhibition of MERS-CoV PLpro by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs.
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Antivirais/farmacologia , Dissulfiram/farmacologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/enzimologia , Peptídeo Hidrolases/metabolismo , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/enzimologia , Dissulfiram/química , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Modelos Moleculares , Conformação Molecular , Peptídeo Hidrolases/química , Peptídeo Hidrolases/genética , Ligação Proteica , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genéticaRESUMO
Single crystals of oxygen-incorporated ZnS (i.e., ZnS(1-x)O x series) are environment-friendly wide-band-gap semiconductors available for light-emitting devices and solar cell use. The series of materials has considerable potential for use in visible ultraviolet areas with flexibility for palette emissions. In this study, we grow oxygen-incorporated ZnS series crystals by chemical vapor transport method with iodine (I2) as the transport agent. Three different oxygen-incorporated crystals of undoped ZnS, ZnS0.94O0.06, and ZnS0.88O0.12 are studied. Through structural studies, ZnS doped with oxygen crystallizes in the main sphalerite phase and a little wurtzite structure. The lattice constants of the major cubic phase are determined to be a = 5.43 Å (ZnS), 5.41 Å (ZnS0.94O0.06), and 5.39 Å (ZnS0.88O0.12). Three band-edge excitonic transitions are simultaneously detected by thermoreflectance measurement for the ZnS, ZnS0.94O0.06, and ZnS0.88O0.12 series samples. The energy positions of the band-edge transitions decrease as the oxygen content increases in the ZnS(1-x)O x series. Defect-state and surface-state emissions, including sulfur vacancy, oxygen vacancy, zinc interstitial, and so forth, can emit approximately full-color spectra from the near band edge of the ZnS(1-x)O x series crystals. With adjusting the oxygen content, the ZnS(1-x)O x can be a series of color-palette luminescence matters that applied for fluorescent display or light-emitting device.