Publications
53 results found
Liu Y, Xu C, Zhou H, et al., 2023, The crystal structures of Sau3AI with and without bound DNA suggest a self-activation-based DNA cleavage mechanism., Structure, Vol: 31, Pages: 1463-1472.e2
The type II restriction endonuclease Sau3AI cleaves the sequence 5'-GATC-3' in double-strand DNA producing two sticky ends. Sau3AI cuts both DNA strands regardless of methylation status. Here, we report the crystal structures of the active site mutant Sau3AI-E64A and the C-terminal domain Sau3AI-C with a bound GATC substrate. Interestingly, the catalytic site of the N-terminal domain (Sau3AI-N) is spatially blocked by the C-terminal domain, suggesting a potential self-inhibition of the enzyme. Interruption of Sau3AI-C binding to substrate DNA disrupts Sau3AI function, suggesting a functional linkage between the N- and C-terminal domains. We propose that Sau3AI-C behaves as an allosteric effector binding one GATC substrate, which triggers a conformational change to open the N-terminal catalytic site, resulting in the subsequent GATC recognition by Sau3AI-N and cleavage of the second GATC site. Our data indicate that Sau3AI and UbaLAI might represent a new subclass of type IIE restriction enzymes.
Yang Y, Hu Z, Kang Y, et al., 2023, Phage SPO1 Protein Gp49 Is a Novel RNA Binding Protein That Is Involved in Host Iron Metabolism, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 24, ISSN: 1661-6596
Liu W, Bi J, Ren Y, et al., 2023, Targeting extracellular CIRP with an X-aptamer shows therapeutic potential in acute pancreatitis, ISCIENCE, Vol: 26
Yang L, Wang J, Lu S, et al., 2023, Temperature-dependent carrier state mediated by H-NS promotes the long-term coexistence of <i>Y</i>. <i>pestis</i> and a phage in soil, PLOS PATHOGENS, Vol: 19, ISSN: 1553-7366
Zhang M, Zhang K, Chen Z, et al., 2023, Secretory expression of human thyroid stimulating hormone receptor A subunit in sf9 insect cell system, Journal of Xi'an Jiaotong University (Medical Sciences), Vol: 44, Pages: 409-414, ISSN: 1671-8259
Objective To construct the secretory expression system of insect cells to express the secretory TSHR A subunit protein in the ovarian cells of Spotoma oryzae (sf9). Methods A recombinant plasmid containing the target protein was constructed, and then the positive bacmid was screened out by the blue and white spots experiment. The verified bacmid was transfected into SF9 insect cells to obtain recombinant baculovirus. The virus was amplified, and the titer level was detected by virus plaque assay. Finally, Western blotting was used to identify the expression of the recombinant protein and optimize the expression conditions. Results During the construction of the protein expression system, PCR identification and sequencing results confirmed the correctness of the sequences of the recombinant plasmid and the recombinant bacmid. After the transfection of the bacmid, the signs of virus budding were observed in sf9 cells. The virus was collected and amplified. The titer of P1 generation virus was 2×107pfu/m according to the plaque assay. The recombinant protein was identified by Western blotting and confirmed to be exogenous into the culture medium. The optimal condition for virus infection and protein expression was 72 h after the infection when the multiplicity of infection (MOI) was 1. Conclusion We constructed an insect cell expression system secreting TSHR 22-289 (55 ku), and the protein could be successfully glycolyzed. This system provides a preliminary basis for the construction and production of its industrial platform and also provides a useful tool for studies on TSHR protein and prevention of GO in the future.
Li L, Zhong Q, Zhao Y, et al., 2023, First-in-human application of double-stranded RNA bacteriophage in the treatment of pulmonary <i>Pseudomonas aeruginosa</i> infection, MICROBIAL BIOTECHNOLOGY, Vol: 16, Pages: 862-867, ISSN: 1751-7915
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- Citations: 1
Li Y, Zhu F, Li Y, et al., 2022, Bacteriophages allow selective depletion of gut bacteria to produce a targeted-bacterium-depleted mouse model, CELL REPORTS METHODS, Vol: 2, ISSN: 2667-2375
Guo R, Gao J, Hui L, et al., 2022, An Improved Method for Quick Quantification of Unsaturated Transferrin, BIOSENSORS-BASEL, Vol: 12
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- Citations: 1
Wang X, Ji Y, Qiu C, et al., 2022, A phage cocktail combined with the enteric probiotic Lactobacillus reuteri ameliorated mouse colitis caused by S. typhimurium., Food Funct, Vol: 13, Pages: 8509-8523
Salmonella enterica serovar Typhimurium (S. typhimurium) is one of the most important foodborne pathogens that causes colitis in humans. In this study, we compared the effects of a therapeutic treatment using a phage cocktail (Pc) in combination or not with Lactobacillus reuteri (L. reuteri) in an S. typhimurium-induced colitis murine model. An oral administration of 4 × 108 CFU per mouse of S. typhimurium resulted in intestinal barrier disruption and severe inflammatory symptoms. S. typhimurium in the colon of the mice treated with the Pc and L. reuteri (PcLR) combination were completely removed compared to those in the single Pc or single L. reuteri treatment groups. Furthermore, compared with the infected group, the intestinal barrier and colonic pathological damage were significantly improved in the PcLR-treated group. Additionally, the short-chain fatty acid (SCFA) levels in the feces of the mice in the PcLR treatment group were significantly increased compared to those in the feces of the mice in the infected group. In addition, the combination of Pc with acetate and reuterin released by L. reuteri (PcReAc) can also achieve the same effect as PcLR treatment. Thus, these results indicated that the acetate and reuterin released by L. reuteri play an important role in the treatment. The extraordinary therapeutic effects of PcLR and PcReAc depend on the specific bactericidal activity of Pc and the broad-spectrum bactericidal activity and immunomodulation of L. reuteri (or acetate and reuterin) in the host. This study provides a new concept for the treatment of inflammatory diseases caused by intestinal pathogens.
Zhang K, Li S, Wang Y, et al., 2022, Bacteriophage protein PEIP is a potent<i> Bacillus</i><i> subtilis</i> enolase inhibitor, CELL REPORTS, Vol: 40, ISSN: 2211-1247
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- Citations: 3
Hou N, Piao X, Jiang N, et al., 2022, Novel Hepatic Schistosomula Antigens as Promising Targets for Immunodiagnosis and Immunoprotection of <i>Schistosomiasis japonica</i>, JOURNAL OF INFECTIOUS DISEASES, Vol: 225, Pages: 1991-2001, ISSN: 0022-1899
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- Citations: 4
Yang H, Yuan H, Zhao X, et al., 2022, Cytoplasmic domain and enzymatic activity of ACE2 are not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells, VIROLOGICA SINICA, Vol: 37, Pages: 380-389, ISSN: 1674-0769
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- Citations: 6
Zhang P, Zhao X, Wang Y, et al., 2022, Bacteriophage protein Gp46 is a cross-species inhibitor of nucleoid-associated HU proteins., Proc Natl Acad Sci U S A, Vol: 119
The architectural protein histone-like protein from Escherichia coli strain U93 (HU) is the most abundant bacterial DNA binding protein and highly conserved among bacteria and Apicomplexan parasites. It not only binds to double-stranded DNA (dsDNA) to maintain DNA stability but also, interacts with RNAs to regulate transcription and translation. Importantly, HU is essential to cell viability for many bacteria; hence, it is an important antibiotic target. Here, we report that Gp46 from bacteriophage SPO1 of Bacillus subtilis is an HU inhibitor whose expression prevents nucleoid segregation and causes filamentous morphology and growth defects in bacteria. We determined the solution structure of Gp46 and revealed a striking negatively charged surface. An NMR-derived structural model for the Gp46-HU complex shows that Gp46 occupies the DNA binding motif of the HU and therefore, occludes DNA binding, revealing a distinct strategy for HU inhibition. We identified the key residues responsible for the interaction that are conserved among HUs of bacteria and Apicomplexans, including clinically significant Mycobacterium tuberculosis, Acinetobacter baumannii, and Plasmodium falciparum, and confirm that Gp46 can also interact with these HUs. Our findings provide detailed insight into a mode of HU inhibition that provides a useful foundation for the development of antibacteria and antimalaria drugs.
Wang M, Wang C, Feng C, et al., 2022, Potent antitumor activity of novel taxoids in anaplastic thyroid cancer., Endocrine, Vol: 75, Pages: 465-477
PURPOSE: Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancers and it is rapidly fatal without any effective therapeutic regimens. There are some clinical trials showing that paclitaxel-based chemotherapy for ATC can achieve a relatively high response rate and low incidence of adverse reaction. The aim of this study was to evaluate potential therapeutic activity of novel taxoids in ATC cells. METHODS: We evaluated antitumor activity of five novel 3'-difluorovinyltaxoids (DFV-taxoids) in anaplastic thyroid cancer cells by a series of in vitro and in vivo experiments. Besides, we also explored the potential mechanism underlying the difference among the taxoids and paclitaxel by molecular docking and tubulin polymerization assays. RESULTS: Our data showed that these novel DFV-taxoids were more effective than paclitaxel in ATC cell lines and xenografts, as reflected by the inhibition of cell proliferation, colony formation and tumorigenic potential in nude mice, and the induction of G2/M phase arrest and cell apoptosis. Using tubulin polymerization assays and molecular docking analysis, we found that these DFV-taxoids promoted more rapid polymerization of β-tubulin than paclitaxel. CONCLUSIONS: Our data demonstrate that these novel taxoids exhibit stronger antitumor activity in ATC cells than paclitaxel, thereby providing a promising therapeutic strategy for the patients with ATC.
Liu D, Xu C, He W, et al., 2021, AutoGenome: An AutoML tool for genomic research, Artificial Intelligence in the Life Sciences, Vol: 1
Deep learning has achieved great successes in traditional fields like computer vision (CV), natural language processing (NLP), speech processing, and more. These advancements have greatly inspired researchers in genomics and made deep learning in genomics an exciting and popular topic. The convolutional neural network (CNN) and recurrent neural network (RNN) are frequently used to solve genomic sequencing and prediction problems, and multiple layer perception (MLP) and auto-encoders (AE) are frequently used for genomic profiling data like RNA expression data and gene mutation data. Here, we introduce a new neural network architecture-the residual fully-connected neural network (RFCN)-and describe its advantage in modeling genomic profiling data. We also incorporate AutoML algorithms and implement AutoGenome, an end-to-end, automated deep learning framework for genomic studies. By utilizing the proposed RFCN architecture, automatic hyper-parameter search, and neural architecture search algorithms, AutoGenome can automatically train high-performance deep learning models for various kinds of genomic profiling data. To help researchers better understand the trained models, AutoGenome can assess the importance of different features and export the most critical features for supervised learning tasks and the representative latent vectors for unsupervised learning tasks. We expect AutoGenome will become a popular tool in genomic studies.
Liu B, Li S, Liu Y, et al., 2021, Bacteriophage Twort protein Gp168 is a β-clamp inhibitor by occupying the DNA sliding channel, NUCLEIC ACIDS RESEARCH, Vol: 49, Pages: 11367-11378, ISSN: 0305-1048
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- Citations: 4
Garnett JA, Palma AS, Liu B, et al., 2021, Editorial: glycans as players in host-microbe interactions: a structural perspective, Frontiers in Molecular Biosciences, Vol: 8, Pages: 1-2, ISSN: 2296-889X
Zhao K, Ke Z, Hu H, et al., 2021, Erratum for Zhao et al., "Structural Basis and Function of the N Terminus of SARS-CoV-2 Nonstructural Protein 1"., Microbiol Spectr, Vol: 9
Zhao K, Ke Z, Hu H, et al., 2021, Structural Basis and Function of the N Terminus of SARS-CoV-2 Nonstructural Protein 1, MICROBIOLOGY SPECTRUM, Vol: 9, ISSN: 2165-0497
Wang Z, Wang H, Mulvenna N, et al., 2021, A bacteriophage DNA mimic protein employs a non-specific strategy to inhibit the bacterial RNA polymerase, Frontiers in Microbiology, Vol: 12, Pages: 1-10, ISSN: 1664-302X
DNA mimicry by proteins is a strategy that employed by some proteins to occupy the binding sites of the DNA-binding proteins and deny further access to these sites by DNA. Such proteins have been found in bacteriophage, eukaryotic virus, prokaryotic, and eukaryotic cells to imitate non-coding functions of DNA. Here, we report another phage protein Gp44 from bacteriophage SPO1 of Bacillus subtilis, employing mimicry as part of unusual strategy to inhibit host RNA polymerase. Consisting of three simple domains, Gp44 contains a DNA binding motif, a flexible DNA mimic domain and a random-coiled domain. Gp44 is able to anchor to host genome and interact bacterial RNA polymerase via the β and β′ subunit, resulting in bacterial growth inhibition. Our findings represent a non-specific strategy that SPO1 phage uses to target different bacterial transcription machinery regardless of the structural variations of RNA polymerases. This feature may have potential applications like generation of genetic engineered phages with Gp44 gene incorporated used in phage therapy to target a range of bacterial hosts.
Zhang K, Li X, Wang Z, et al., 2021, Systemic Expression, Purification, and Initial Structural Characterization of Bacteriophage T4 Proteins Without Known Structure Homologs, FRONTIERS IN MICROBIOLOGY, Vol: 12, ISSN: 1664-302X
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- Citations: 2
Li Y, Li G, Wang Z, et al., 2021, Resonance assignments of the cytoplasmic domain of ECF sigma factor W pathway protein YsdB from <i>Bacillus subtilis</i>, BIOMOLECULAR NMR ASSIGNMENTS, Vol: 15, Pages: 103-106, ISSN: 1874-2718
Wang Z, Zhao S, Li Y, et al., 2021, RssB-mediated σ<SUP>S</SUP> Activation is Regulated by a Two-Tier Mechanism via Phosphorylation and Adaptor Protein - IraD, JOURNAL OF MOLECULAR BIOLOGY, Vol: 433, ISSN: 0022-2836
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- Citations: 3
Xu C, Ke Z, Liu C, et al., 2020, Systemic <i>In Silico</i> Screening in Drug Discovery for Coronavirus Disease (COVID-19) with an Online Interactive Web Server, JOURNAL OF CHEMICAL INFORMATION AND MODELING, Vol: 60, Pages: 5735-5745, ISSN: 1549-9596
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- Citations: 17
Zhu F, Guo R, Wang W, et al., 2020, Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice, MOLECULAR PSYCHIATRY, Vol: 25, Pages: 2905-2918, ISSN: 1359-4184
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- Citations: 135
Yang Y, Ke Z, Wang Z, et al., 2020, <SUP>1</SUP>H, <SUP>13</SUP>C and <SUP>15</SUP> N NMR assignments of solubility tag protein Msyb of <i>Escherichia coli</i>, BIOMOLECULAR NMR ASSIGNMENTS, Vol: 14, Pages: 251-254, ISSN: 1874-2718
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- Citations: 2
Krishna A, Liu B, Peacock SJ, et al., 2020, The prevalence and implications of single-nucleotide polymorphisms in genes encoding 3 the RNA polymerase of clinical isolates of Staphylococcus aureus, MicrobiologyOpen, Vol: 9, Pages: 1-8, ISSN: 2045-8827
Central to the regulation of bacterial gene expression is the multisubunit enzyme RNA polymerase (RNAP), which is responsible for catalyzing transcription. As all adaptive processes are underpinned by changes in gene expression, the RNAP can be considered the major mediator of any adaptive response in the bacterial cell. In bacterial pathogens, theoretically, single nucleotide polymorphisms (SNPs) in genes that encode subunits of the RNAP and associated factors could mediate adaptation and confer a selective advantage to cope with biotic and abiotic stresses. We investigated this possibility by undertaking a systematic survey of SNPs in genes encoding the RNAP and associated factors in a collection of 1,429 methicillin‐resistant Staphylococcus aureus (MRSA) clinical isolates. We present evidence for the existence of several, hitherto unreported, nonsynonymous SNPs in genes encoding the RNAP and associated factors of MRSA ST22 clinical isolates and propose that the acquisition of amino acid substitutions in the RNAP could represent an adaptive strategy that contributes to the pathogenic success of MRSA.
Zhang K, Wang Z, Chang G, et al., 2020, Resonance assignments of bacteriophage T4 Y04L protein, BIOMOLECULAR NMR ASSIGNMENTS, Vol: 14, Pages: 51-54, ISSN: 1874-2718
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- Citations: 2
Wang Z, Liang Y, Liu H, et al., 2020, Resonance assignments of bacteriophage SPO1 Gp49 protein, BIOMOLECULAR NMR ASSIGNMENTS, Vol: 14, Pages: 111-114, ISSN: 1874-2718
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- Citations: 2
Wang Z, Zhao S, Jiang S, et al., 2019, Resonance assignments of N-terminal receiver domain of sigma factor S regulator RssB from <i>Escherichia coli</i>, BIOMOLECULAR NMR ASSIGNMENTS, Vol: 13, Pages: 333-337, ISSN: 1874-2718
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- Citations: 1
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