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3D nanoprinting can significantly enhance the performance of sensors, batteries, optoelectronic/microelectronic devices, etc. However, current 3D nanoprinting methods for metal oxides are suffering from three key issues including limited material applicability, serious shape distortion, and the difficulty of heterogeneous integration. This paper discovers a mechanism in which imidazole and acrylic acid synergistically coordinate with metal ions in water. Using the mechanism, this work develops a series of metal ion synergistic coordination water-soluble (MISCWS) resins for 3D nanoprinting of various metal oxides, including MnO2, Cr2O3, Co3O4, and ZnO, as well as heterogeneous structures of MnO2/NiO, Cr2O3/Al2O3, and ZnO/MgO. Besides, the synergistic coordination effect results in a 2.54-fold increase in inorganic mass fraction within the polymer, compared with previous works, which effectively mitigates the shape distortion of metal oxide microstructures. Based on this method, this work also demonstrates a 3D ZnO microsensor with a high sensitivity (1.113 million at 200 ppm NO2), surpassing the conventional 2D ZnO sensors by tenfold. The method yields high-fidelity 3D structures of heterogeneous metal oxides with nanoscale resolution, paving the way for applications such as sensing, micro-optics, energy storage, and microsystems.
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Solar-light photosynthesis of ammonia form N2 reduction in ultrapure water over the artificial photocatalysts is attractive but still challenging compared with Haber-Bosch process. In this work, ultrathin Fe-Ta2O5-x nanobelts were fabricated via the controllable solvothermal process for ammonia photosynthesis. The formed oxygen vacancies and Fe doping narrowed their bandgap energies and promoted the carriers' separation and transfer for Fe-Ta2O5-x nanobelts. In addition, Fe doping also resulted in the reduced working functions of the samples, indicating a weaker electron binding restriction and stronger separation and transfer of photo-induced carriers. The experimental results showed that Fe-Ta2O5-x nanobelts showed remarkably enhanced photocatalytic ammonia production performance under simulated sunlight irradiation, and the relevant ammonia production rate reached approximately 3030.86 µM g-1 h-1, which was 9.63 times of pristine Ta2O5-x and 491.0 times of commercial Ta2O5, and a relatively stable photocatalytic ammonia production performance under simulated sunlight irradiation for Fe-Ta2O5-x nanobelts. Meanwhile, it was also found that Fe doping has great influences on the photocatalytic performance under visible light and simulated sunlight irradiation, mainly because of their suitable bandgap energies and enhanced solar-light harvesting capacity. Current work indicates the great potentials of ultrathin tantalum-based functional materials for high-efficiency ammonia photosynthesis.
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Understanding changes in pathogen behavior (e.g. increased virulence, a shift in transmission channel) is critical for the public health management of emerging infectious diseases. Genome degradation via gene depletion or inactivation is recognized as a pathoadaptive feature of the pathogen evolving with the host. However, little is known about the exact role of genome degradation in affecting pathogenic behavior, and the underlying molecular detail has yet to be examined. Using large-scale global avian-restricted Salmonella genomes spanning more than a century, we projected the genetic diversity of Salmonella Pullorum (bvSP) by showing increasingly antimicrobial-resistant ST92 prevalent in Chinese flocks. The phylogenomic analysis identified three lineages in bvSP, with an enhancement of virulence in the two recently emerged lineages (L2/L3), as evidenced in chicken and embryo infection assays. Notably, the ancestor L1 lineage resembles the Salmonella serovars with higher metabolic flexibilities and more robust environmental tolerance, indicating stepwise evolutionary trajectories towards avian-restricted lineages. Pan-genome analysis pinpointed fimbrial degradation from a virulent lineage. The later engineered fim-deletion mutant, and all other five fimbrial systems, revealed behavior switching that restricted horizontal fecal-oral transmission but boosted virulence in chicks. By depleting fimbrial appendages, bvSP established persistent replication with less proinflammation in chick macrophages and adopted vertical transovarial transmission, accompanied by ever-increasing intensification in the poultry industry. Together, we uncovered a previously unseen paradigm for remodeling bacterial surface appendages that supplements virulence-enhanced evolution with increased vertical transmission.
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Biological energy currency ATP is produced by F1Fo-ATP synthase. However, the molecular mechanism for human ATP synthase action remains unknown. Here, we present snapshot images for three main rotational states and one substate of human ATP synthase using cryoelectron microscopy. These structures reveal that the release of ADP occurs when the ß subunit of F1Fo-ATP synthase is in the open conformation, showing how ADP binding is coordinated during synthesis. The accommodation of the symmetry mismatch between F1 and Fo motors is resolved by the torsional flexing of the entire complex, especially the γ subunit, and the rotational substep of the c subunit. Water molecules are identified in the inlet and outlet half-channels, suggesting that the proton transfer in these two half-channels proceed via a Grotthus mechanism. Clinically relevant mutations are mapped to the structure, showing that they are mainly located at the subunit-subunit interfaces, thus causing instability of the complex.
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Trifosfato de Adenosina , ATPases Translocadoras de Prótons , Humanos , Microscopia Crioeletrônica , Trifosfato de Adenosina/metabolismo , ATPases Translocadoras de Prótons/química , Conformação ProteicaRESUMO
Human complex II is a key protein complex that links two essential energy-producing processes: the tricarboxylic acid cycle and oxidative phosphorylation. Deficiencies due to mutagenesis have been shown to cause mitochondrial disease and some types of cancers. However, the structure of this complex is yet to be resolved, hindering a comprehensive understanding of the functional aspects of this molecular machine. Here, we have determined the structure of human complex II in the presence of ubiquinone at 2.86 Å resolution by cryoelectron microscopy, showing it comprises two water-soluble subunits, SDHA and SDHB, and two membrane-spanning subunits, SDHC and SDHD. This structure allows us to propose a route for electron transfer. In addition, clinically relevant mutations are mapped onto the structure. This mapping provides a molecular understanding to explain why these variants have the potential to produce disease.
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Estrutura Quaternária de Proteína , Humanos , Modelos Moleculares , Mutação , Microscopia CrioeletrônicaRESUMO
Salmonella enterica serovar Gallinarum biovar Gallinarum is an avian-adapted pathogen causing fowl typhoid and leading to enormous economic loss in the global poultry industry. Two-component systems (TCSs) are crucial for bacteria survival, virulence, sensing and responding to the environment. 23 pairs of TCSs classified into five families were found in S. Gallinarum strain 287/91, of which the CitB family contains three pairs of TCSs, namely CitA/CitB, DcuS/DcuR and DpiB/DpiA, whose functions remained unaddressed. Thus, four mutants of S. Gallinarum strain U20, ΔcitAB (Δcit), ΔdcuSR (Δdcu), ΔdpiBA (Δdpi) and ΔcitABΔdcuSRΔdpiBA (Δ3), were constructed. The results suggested that the CitB family did not affect the growth or the metabolic capacities tested, while different TCSs exerted various effects on biofilm formation and antimicrobial resistance against multiple drug classes. Furthermore, the CitB family negatively impacted the tolerance of environmental stress, contributing to compromised virulence in chicken embryos and in vivo survival of S. Gallinarum. Collectively, this research provided new knowledge of how the CitB family is involved in the pathogenicity of S. Gallinarum.
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Doenças das Aves Domésticas , Salmonelose Animal , Salmonella enterica , Embrião de Galinha , Animais , Salmonella enterica/genética , Sorogrupo , Salmonella , Virulência/genética , Salmonelose Animal/microbiologia , Galinhas , Doenças das Aves Domésticas/microbiologiaRESUMO
The emergence and dissemination of the extended spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae harbouring antimicrobial resistance (AMR) genes has diminished the potential options for treating multidrug-resistant (MDR) bacterial infections. Until now, numerous studies reported the spreading of critical plasmid-borne AMR genes from different sources worldwide. While the knowledge on the occurrence of the plasmid-borne AMR genes, especially mcr genes in the dead chick embryos, remains obscure. A retrospective study was conducted to detect the presence of the mcr genes in forty-five Salmonella enterica isolates recovered from 2139 dead chick embryo samples, from breeding chicken hatcheries in Henan, China. Using multiplex PCR, we found only four isolates out of the forty-five were mcr-9-positive. These four isolates were found to be MDR, ESBL- producing and showed resistance to 10 antimicrobial drugs. Additionally, mcr-9 harbouring plasmids were successfully transferred into Escherichia coli (E. coli) J53 by conjugation and the mcr-9 gene was confirmed by PCR. We also found that the transconjugants exhibited higher MICs for ampicillin, gentamycin and colistin than the recipient. Whole-genome sequence analysis showed that the four isolates belonged to Salmonella Thompson ST26 and harboured IncHI2 plasmid replicon. Furthermore, the mcr-9 harbouring plasmids were reconstructed using in silico tools and found to be carried other AMR genes (blaDHA-1 and qnrB4). The studied isolates carried the typical virulence factors from Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2), in addition to pef and csg operons which are important in host adhesion and biofilm formation. The mgtC gene, which is involved in phagocytosis, has also been identified. Together, the increase in the phenotypic resistance of the transconjugants and the plasmid in silico reconstruction analysis confirmed that the corresponding resistance genes might be located together on the same plasmid. To track the potential phylogenomic relations of our detected ESBL S. Thompson isolates, we constructed a phylogenomic tree with available ESBL S. Thompson genomes (n = 26) that were reported worldwide. The studied isolates were independently clustered together with four other Chinese isolates of food origin in one clade, providing strong evidence of a potential recent and wide dissemination of ESBL S. Thompson across the food chain in China. In conclusion, we report the detection of four highly virulent ESBL-producing S. Thompson ST26 isolates harbouring mcr-9 gene obtained from dead chick embryos in Henan, China.
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Proteínas de Escherichia coli , Escherichia coli , Embrião de Galinha , Animais , Escherichia coli/genética , Antibacterianos/farmacologia , Proteínas de Escherichia coli/genética , Estudos Retrospectivos , Colistina , Plasmídeos/genética , Salmonella/genética , Enterobacteriaceae/genética , Genômica , beta-Lactamases/genética , Testes de Sensibilidade Microbiana/veterináriaRESUMO
Our demand for ubiquitous and reliable gas detection is spurring the design of intelligent and enabling gas sensors for the next-generation Internet of Things and Artificial Intelligence. The desire to introduce gas sensors everywhere is fueled by opportunities to create room-temperature semiconductor gas sensors with ultralow power consumption. In this Perspective, we provide an overview of the recent achievement of room-temperature gas sensors that have been translated from the advances in the design of the chemical and physical properties of low-dimensional semiconductor nanomaterials. The emergence of solution-processable nanomaterials opens up remarkable opportunities to integrate into high-performance and flexible room-temperature gas sensors by using low-temperature, large-area, solution-based methods instead of costly, high-vacuum, high-temperature device manufacturing processes. We review the fundamental factors which affect the receptor and transducer functions of semiconductor gas sensors. We also discuss challenges that must be addressed in the move to the continuous miniaturization and evolution of semiconductor gas sensors.
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Inteligência Artificial , Temperatura Baixa , Temperatura , Internet , SemicondutoresRESUMO
Invasive nontyphoidal Salmonella (iNTS) causes extraintestinal infections with ~15% case fatality in many countries. However, the mechanism by which iNTS emerged in China remains unaddressed. We conducted clinical investigations of iNTS infection with recurrent treatment failure, caused by underreported Salmonella enterica serovar Livingstone (SL). Genomic epidemiology demonstrated five clades in the SL population and suggested that the international animal feed trade was a likely vehicle for their introduction into China, as evidenced by multiple independent transmission incidents. Importantly, isolates from Clade-5-I-a/b, predominant in China, showed an invasive nature in mice, chicken and zebrafish infection models. The antimicrobial susceptibility testing revealed most isolates (> 96%) in China are multidrug-resistant (MDR). Overall, we offer exploiting genomics in uncovering international transmission led by the animal feed trade and highlight an emerging hypervirulent clade with increased resistance to frontline antibiotics.
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Domesticação , Infecções por Salmonella , Animais , Camundongos , Sorogrupo , Peixe-Zebra , Infecções por Salmonella/epidemiologia , Salmonella/genética , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genéticaRESUMO
Salmonella enterica, serovar Gallinarum, biovar Pullorum, is an avian-specific pathogen which has caused considerable economic losses to the poultry industry worldwide. Two-component systems (TCSs) play an essential role in obtaining nutrients, detecting the presence of neighboring bacteria and regulating the expression of virulence factors. The genome analysis of S. Pullorum strain S06004 suggesting the carriage of 22 pairs of TCSs, which belong to five families named CitB, OmpR, NarL, Chemotaxis and LuxR. In the CitB family, three pairs of TCSs, namely CitA-CitB, DcuS-DcuR and DpiB-DpiA, remain unaddressed in S. Pullorum. To systematically investigate the function of the CitB family in S. Pullorum, four mutants, ΔcitAB (abbreviated as Δcit), ΔdcuSR (Δdcu), ΔdpiBA (Δdpi) and ΔcitABΔdcuSRΔdpiBA (Δ3), were made using the CRISPR/Cas9 system. The results demonstrated that the CitB family did not affect the growth of bacteria, the results of biochemical tests, invasion and proliferation in chicken macrophage HD-11 cells and the expression of fimbrial protein. But the mutants showed thicker biofilm formation, higher resistance to antimicrobial agents, enhanced tolerance to inhibition by egg albumen and increased virulence in chicken embryos. Moreover, the deletion of Dpi TCS was detrimental to survival after exposure to hyperosmotic and oxidative environments, as well as the long-term colonization of the small intestine of chickens. Collectively, we provided new knowledge regarding the possible role of the CitB family involved in the pathogenic processes of S. Pullorum.
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Doenças das Aves Domésticas , Salmonelose Animal , Salmonella enterica , Animais , Embrião de Galinha , Galinhas/microbiologia , Doenças das Aves Domésticas/microbiologia , Salmonella/genética , Salmonelose Animal/microbiologiaRESUMO
Pathogenic mycobacteria pose a sustained threat to global human health. Recently, cytochrome bcc complexes have gained interest as targets for antibiotic drug development. However, there is currently no structural information for the cytochrome bcc complex from these pathogenic mycobacteria. Here, we report the structures of Mycobacterium tuberculosis cytochrome bcc alone (2.68 Å resolution) and in complex with clinical drug candidates Q203 (2.67 Å resolution) and TB47 (2.93 Å resolution) determined by single-particle cryo-electron microscopy. M. tuberculosis cytochrome bcc forms a dimeric assembly with endogenous menaquinone/menaquinol bound at the quinone/quinol-binding pockets. We observe Q203 and TB47 bound at the quinol-binding site and stabilized by hydrogen bonds with the side chains of QcrBThr313 and QcrBGlu314, residues that are conserved across pathogenic mycobacteria. These high-resolution images provide a basis for the design of new mycobacterial cytochrome bcc inhibitors that could be developed into broad-spectrum drugs to treat mycobacterial infections.
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Antituberculosos/farmacologia , Proteínas de Bactérias/química , Citocromos/química , Imidazóis/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Piperidinas/farmacologia , Piridinas/farmacologia , Microscopia Crioeletrônica , Desenvolvimento de MedicamentosRESUMO
Salmonella spp. is recognized as an important zoonotic pathogen. The emergence of antimicrobial resistance in Salmonella enterica poses a great public health concern worldwide. While the knowledge on the incidence and the characterization of different S. enterica serovars causing chick embryo death remains obscure in China. In this study, we obtained 45 S. enterica isolates from 2,139 dead chick embryo samples collected from 28 breeding chicken hatcheries in Henan province. The antimicrobial susceptibility assay was performed by the broth microdilution method and the results showed that 31/45 (68.8%) isolates were multidrug-resistant (≥3 antimicrobial classes). Besides the highest resistance rate was observed in the aminoglycoside class, all the isolates were susceptible to chloramphenicol, azithromycin, and imipenem. Furthermore, genomic characterization revealed that S. Enteritidis (33.33%; 15/45) was a frequent serovar that harbored a higher number of virulence factors compared to other serovars. Importantly, genes encoding ß-lactamases were identified in three serovars (Thompson, Enteritidis, and Kottbus), whereas plasmid-mediated quinolone resistance genes (qnrB4) were detected in certain isolates of S. Thompson and the two S. Kottbus isolates. All the examined isolates harbored the typical virulence factors from Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2). Additionally, a correlation analysis between the antimicrobial resistance genes, phenotype, and plasmids was conducted among Salmonella isolates. It showed strong positive correlations (r < 0.6) between the different antimicrobial-resistant genes belonging to certain antimicrobial classes. Besides, IncF plasmid showed a strong negative correlation (r > -0.6) with IncHI2 and IncHI2A plasmids. Together, our study demonstrated antimicrobial-resistant S. enterica circulating in breeding chicken hatcheries in Henan province, highlighting the advanced approach, by using genomic characterization and statistical analysis, in conducting the routine monitoring of the emerging antimicrobial-resistant pathogens. Our findings also proposed that the day-old breeder chicks trading could be one of the potential pathways for the dissemination of multidrug-resistant S. enterica serovars.
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Cytochromes bd are ubiquitous amongst prokaryotes including many human-pathogenic bacteria. Such complexes are targets for the development of antimicrobial drugs. However, an understanding of the relationship between the structure and functional mechanisms of these oxidases is incomplete. Here, we have determined the 2.8 Å structure of Mycobacterium smegmatis cytochrome bd by single-particle cryo-electron microscopy. This bd oxidase consists of two subunits CydA and CydB, that adopt a pseudo two-fold symmetrical arrangement. The structural topology of its Q-loop domain, whose function is to bind the substrate, quinol, is significantly different compared to the C-terminal region reported for cytochromes bd from Geobacillus thermodenitrificans (G. th) and Escherichia coli (E. coli). In addition, we have identified two potential oxygen access channels in the structure and shown that similar tunnels also exist in G. th and E. coli cytochromes bd. This study provides insights to develop a framework for the rational design of antituberculosis compounds that block the oxygen access channels of this oxidase.
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Proteínas de Bactérias/ultraestrutura , Microscopia Crioeletrônica/métodos , Grupo dos Citocromos b/ultraestrutura , Complexo de Proteínas da Cadeia de Transporte de Elétrons/ultraestrutura , Mycobacterium smegmatis/enzimologia , Oxirredutases/ultraestrutura , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Grupo dos Citocromos b/química , Grupo dos Citocromos b/metabolismo , Transporte de Elétrons , Complexo de Proteínas da Cadeia de Transporte de Elétrons/química , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Heme/química , Heme/metabolismo , Modelos Moleculares , Mycobacterium smegmatis/genética , Oxirredutases/química , Oxirredutases/metabolismo , Oxigênio/metabolismo , Conformação Proteica , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestrutura , Especificidade por SubstratoRESUMO
Fibroblast growth factor receptors (FGFRs) have become promising therapeutic targets in various types of cancers. In fact, several selective irreversible inhibitors capable of covalently reacting with the conserved cysteine of FGFRs are currently being evaluated in clinical trials. In this article, we optimized and discovered a novel lead compound 36 with remarkable inhibitory effects against FGFR (1-3), which is a derivative of 2H-pyrazolo[3,4-d]pyrimidine. The irreversible binding to FGFRs was characterized by LC-MS. This compound has been shown to exhibit significant anti-proliferation effects against NCI-H1581 and SNU-16 cancer cell lines both in vitro and in vivo. Compound 36 has also demonstrated a low toxicity profile and adequate pharmacokinetic properties and is currently under validation as a potential drug candidate.
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Antineoplásicos/farmacologia , Descoberta de Drogas , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirazóis/síntese química , Pirazóis/química , Pirimidinas/síntese química , Pirimidinas/química , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Mesocrystals are types of fascinating multifunctional materials in fabricating rapid charge transport pathways, and surface engineering could be considered as a significant influencing factor in boosting charge separation for efficient photocatalytic application. In this work, surface engineered Ta2O5-x mesocrystals were synthesized by facile alkali treatment strategy for enhanced visible light photocatalytic tetracycline degradation. The highly enhanced photocatalytic activity could be attributed to the highly increased surface areas and surface hydroxyl groups to compare with those of commercial Ta2O5 and pristine Ta2O5-x mesocrystals, which could provide more surface reactive sites and high electron density center for trapping photo-generated holes. Besides, possible tetracycline transformation pathways over surface engineered Ta2O5-x mesocrystals and visible light photocatalytic mechanism were also proposed in this work. Current work also provides a facile strategy for regulating surface property of ultrawide bandgaps semiconductors for enhanced visible light photocatalytic performance.
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Luz , Tetraciclina , Antibacterianos , Catálise , Propriedades de SuperfícieRESUMO
Encapsulins containing dye-decolorizing peroxidase (DyP)-type peroxidases are ubiquitous among prokaryotes, protecting cells against oxidative stress. However, little is known about how they interact and function. Here, we have isolated a native cargo-packaging encapsulin from Mycobacterium smegmatis and determined its complete high-resolution structure by cryogenic electron microscopy (cryo-EM). This encapsulin comprises an icosahedral shell and a dodecameric DyP cargo. The dodecameric DyP consists of two hexamers with a twofold axis of symmetry and stretches across the interior of the encapsulin. Our results reveal that the encapsulin shell plays a role in stabilizing the dodecameric DyP. Furthermore, we have proposed a potential mechanism for removing the hydrogen peroxide based on the structural features. Our study also suggests that the DyP is the primary cargo protein of mycobacterial encapsulins and is a potential target for antituberculosis drug discovery.
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Proteínas de Bactérias/ultraestrutura , Mycobacterium smegmatis/ultraestrutura , Peroxidases/ultraestrutura , Proteínas de Bactérias/metabolismo , Microscopia Crioeletrônica/métodos , Mycobacterium smegmatis/metabolismo , Mycobacterium smegmatis/patogenicidade , Organelas/metabolismo , Organelas/fisiologia , Peroxidases/metabolismoRESUMO
Complex II, also known as succinate dehydrogenase (SQR) or fumarate reductase (QFR), is an enzyme involved in both the Krebs cycle and oxidative phosphorylation. Mycobacterial Sdh1 has recently been identified as a new class of respiratory complex II (type F) but with an unknown electron transfer mechanism. Here, using cryoelectron microscopy, we have determined the structure of Mycobacterium smegmatis Sdh1 in the presence and absence of the substrate, ubiquinone-1, at 2.53-Å and 2.88-Å resolution, respectively. Sdh1 comprises three subunits, two that are water soluble, SdhA and SdhB, and one that is membrane spanning, SdhC. Within these subunits we identified a quinone-binding site and a rarely observed Rieske-type [2Fe-2S] cluster, the latter being embedded in the transmembrane region. A mutant, where two His ligands of the Rieske-type [2Fe-2S] were changed to alanine, abolished the quinone reduction activity of the Sdh1. Our structures allow the proposal of an electron transfer pathway that connects the substrate-binding and quinone-binding sites. Given the unique features of Sdh1 and its essential role in Mycobacteria, these structures will facilitate antituberculosis drug discovery efforts that specifically target this complex.
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Proteínas de Bactérias/química , Complexo III da Cadeia de Transporte de Elétrons/química , Flavoproteínas/química , Mycobacterium tuberculosis/enzimologia , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Microscopia Crioeletrônica , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Flavoproteínas/metabolismo , Simulação de Dinâmica Molecular , Ligação Proteica , Ubiquinona/química , Ubiquinona/metabolismoRESUMO
Diheme-containing succinate:menaquinone oxidoreductases (Sdh) are widespread in Gram-positive bacteria but little is known about the catalytic mechanisms they employ for succinate oxidation by menaquinone. Here, we present the 2.8 Å cryo-electron microscopy structure of a Mycobacterium smegmatis Sdh, which forms a trimer. We identified the membrane-anchored SdhF as a subunit of the complex. The 3 kDa SdhF forms a single transmembrane helix and this helix plays a role in blocking the canonically proximal quinone-binding site. We also identified two distal quinone-binding sites with bound quinones. One distal binding site is formed by neighboring subunits of the complex. Our structure further reveals the electron/proton transfer pathway for succinate oxidation by menaquinone. Moreover, this study provides further structural insights into the physiological significance of a trimeric respiratory complex II. The structure of the menaquinone binding site could provide a framework for the development of Sdh-selective anti-mycobacterial drugs.
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Proteínas de Bactérias/química , Mycobacterium smegmatis/enzimologia , Succinato Desidrogenase/química , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Catálise , Microscopia Crioeletrônica , Transporte de Elétrons , Modelos Moleculares , Complexos Multienzimáticos/química , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Mycobacterium smegmatis/química , Oxirredução , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Relação Estrutura-Atividade , Succinato Desidrogenase/metabolismo , Ácido Succínico/metabolismo , Vitamina K 2/metabolismoRESUMO
Harvesting broad spectral absorption and visible light photocatalysis of ultrawide bandgap semiconductors are one of most significative topics in the solar energy conversion and utilization fields. In this work, amorphous Cl-Ta2O5-x microspheres were prepared by facile solvothermal method for stabilized visible light photocatalytic hydrogen generation. The acetone absorbed on the interfaces of Ta2O5 nanoparticles induced the formation of oxygen vacancies, enhanced visible light absorption, and formation of Ta2O5-x microspheres with preferred orientations as well as Cl doping. The Cl-Ta2O5-x microspheres showed typical amorphous characteristics and obvious visible light absorption in comparison to those of commercial Ta2O5. More importantly, the prepared Cl-Ta2O5-x microspheres also showed stabilized visible light photocatalytic hydrogen generation performance in the spectral regions of 400 nm ≤ λ ≤ 600 nm mainly because of the introduction of oxygen vacancy defects and Cl doping, which might significantly expand the application of tantalum oxide semiconductors in the broad spectral photocatalytic water splitting.