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An octamer of enolase from Streptococcus suis

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Protein & Cell 2012年第10期3卷 769-780页

作者： Qiong lu Hao lu Jianxun Qi guangwen lu George F Gao CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Graduate University Chinese Academy of SciencesBeijing 100049China Research Network of Immunity and Health(RNIH) Beijing Institutes of Life ScienceChinese Academy of SciencesBeijing 100101China Laboratory of Protein Engineering and Vaccines Tianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjin 300308China

Enolase is a conserved cytoplasmic metalloenzyme existing universally in both eukaryotic and prokaryotic *** enzyme can also locate on the cell surface and bind to plasminogen,via which contributing to the mucosal surface localization of the bacterial pathogens and assisting the invasion into the host *** functions of the eukaryotic enzymes on the cell surface expression(including T cells,B cells,neutrophils,monocytoes,neuronal cells and epithelial cells)are not *** suis serotype 2(*** 2,SS2)is an important zoonotic pathogen which has recently caused two large-scale outbreaks in southern China with severe streptococcal toxic shock syndrome(STSS)never seen before in human *** recently identified the SS2 enolase as an important protective antigen which could protect mice from fatal *** 2 *** this study,a 2.4-angstrom structure of the SS2 enolase is solved,revealing an octameric arrangement in the *** further demonstrated that the enzyme exists exclusively as an octamer in solution via a sedimentation *** results indicate that the octamer is the biological unit of SS2 enolase at least in vitro and most likely in vivo as *** is,to our knowledge,the first comprehensive characterization of the SS2 enolase octamer both structurally and biophysically,and the second octamer enolase structure in addition to that of Streptococcus *** also investigated the plasminogen binding property of the SS2 enzyme.

关键词： enolase octamer Streptococcus suis structure plasminogen binding

Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines

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Signal Transduction and Targeted Therapy 2023年第6期8卷 2577-2598页

作者： Liyan Guo Sheng Lin Zimin Chen Yu Cao Bin He guangwen lu Department of Emergency Medicine State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China Disaster Medicine Center West China HospitalSichuan UniversityChengduSichuan610041China

The ongoing global pandemic of coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),has caused devastating impacts on the public health and the global *** viral antigenic evolution has led to the continual generation of new *** special note is the recently expanding Omicron subvariants that are capable of immune evasion from most of the existing neutralizing antibodies(nAbs).This has posed new challenges for the prevention and treatment of ***,exploring broad-spectrum antiviral agents to combat the emerging variants is *** sharp contrast to the massive accumulation of mutations within the SARS-CoV-2 receptor-binding domain(RBD),the S2 fusion subunit has remained highly conserved among ***,S2-based therapeutics may provide effective cross-protection against new SARS-CoV-2 ***,we summarize the most recently developed broad-spectrum fusion inhibitors(e.g.,nAbs,peptides,proteins,and small-molecule compounds)and candidate vaccines targeting the conserved elements in SARS-CoV-2 S2 *** main focus includes all the targetable S2 elements,namely,the fusion peptide,stem helix,and heptad repeats 1 and 2(HR1-HR2)***,we provide a detailed summary of the characteristics and action-mechanisms for each class of cross-reactive fusion inhibitors,which should guide and promote future design of S2-based inhibitors and vaccines against new coronaviruses.

关键词： vaccines prevention elements

Nanopores/Nanochannels Based on Electrical and Optical Dual Signal Response for Application in Biological Detection

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Chinese Journal of Chemistry 2023年第11期41卷 1374-1384页

作者： guangwen lu Niya Lin Zhaojun Chen Wenlian Jiang Jing-Jing Hu Fan Xia Xiaoding Lou State Key Laboratory of Biogeology and Environmental Geology Faculty of Materials Science and ChemistryChina University of GeosciencesWuhanHubei430078 China

Cancers and chronic diseases have always been global health problems. The occurrence and development of such diseases are closely related to the abnormalities of proteins, nucleic acids, ions or small molecules in the body. Nowadays, nanopores/nanochannels have emerged as a powerful platform for detecting these biomolecules based on the electrical signal variation caused by biomolecules passing. However, detection relied on the electrical signal easily suffered from the clogging defects, low throughput, and strong background signals. Fortunately, the emergence of designing nanopores/nanochannels based on electrical and optical dual signal response has brought innovative impetus to biological detection, which can also identify the chemical compositions and conformations of the biomolecules. In this review, we summarize the reasonable preparation of nanopores/nanochannels with electrical and optical dual signal response and their application in biological detection. According to different biomolecules, we divide the targets into four types, including nucleic acids, small molecules, ions and proteins. In each section, the design of representative examples and the principle of dual signal generation are introduced and discussed. Finally, the prospects and challenges of nanopores/nanochannels based on electrical and optical dual signal response are also discussed.

关键词： Biomolecules Nanopores nanochannels Electrical and optical Fluorescence lon current

In vitro Transcriptome Analysis of Two Chinese Isolates of Streptococcus suis Serotype 2

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Genomics, Proteomics & Bioinformatics 2014年第6期12卷 266-275页

作者： Dake Zhang Nan Du Sufang Ma Qingtao Hu guangwen lu Wei Chen Changqing Zeng CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences University of Chinese Academy of Sciences

The Streptococcus suis serotype 2（S. suis 2） isolates 05ZYH33 and 98HAH33 have caused severe human infections in China. Using a strand-specific RNA-seq analysis, we compared the in vitro transcriptomes of these two Chinese isolates with that of a reference strain（P1/7）. In the89 K genomic island that is specific to these Chinese isolates, a toxin–antitoxin system showed relatively high levels of transcription among the S. suis. The known virulence factors with high transcriptional activity in these two highly-pathogenic strains are mainly involved in adhesion, biofilm formation, hemolysis and the synthesis and transport of the outer membrane protein. Furthermore,our analysis of novel transcripts identified over 50 protein-coding genes with one of them encoding a toxin protein. We also predicted over 30 small RNAs（s RNAs） in each strain, and most of them are involved in riboswitches. We found that six s RNA candidates that are related to bacterial virulence, including csp A and rli38, are specific to Chinese isolates. These results provide insight into the factors responsible for the difference in virulence among the different S. suis 2 isolates.

关键词： Streptococcus suis serotype 2 Transcriptome Novel transcripts s RNA Virulence factor

Gluconate 5-dehydrogenase （Ga5DH） participates in Streptococcus suis cell division

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Protein & Cell 2014年第10期5卷 761-769页

作者： Zhongyu Shi Chunling Xuan Huiming Han Xia Cheng Jundong Wang Youjun Feng Swaminath Srinivass guangwen lu George F. Gao CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of SciencesBeijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China College of Animal Science and Technology Shanxi Agricultural University Taigu 030801 China Department of Microbiology University of Illinois Urbana IL 61801 USA Department of Biochemistry University of Illinois Urbana IL 6180 USA Laboratory of Protein Engineering and Vaccines Tianjin Institute of Industrial Biotechnology Chinese Academy of SciencesTianjin 300308 China Research Network of Immunity and Health (RNIH) Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100101 China

Bacterial cell division is strictly regulated in the formation of equal daughter cells. This process is governed by a series of spatial and temporal regulators, and several new factors of interest to the field have recently been identified. Here, we report the requirement of gluconate 5-dehydrogenase （Ga5DH） in cell division of the zoonotic pathogen Strepto- coccus suis. GaSDH catalyzes the reversible reduction of 5-ketogluconate to D-gluconate and was localized to the site of cell division. The deletion of Ga5DH in S. suis resulted in a plump morphology with aberrant septa joining the progeny. A significant increase was also observed in cell length. These defects were determined to be the conse- quence of Ga5DH deprivation in S. suis causing FtsZ delo- calization. In addition, the interaction of FtsZ with Ga5DH in vitro was confirmed by protein interaction assays. These results indicate that GaSDH may function to prevent the formation of ectopic Z rings during S. suis cell division.

关键词： Streptococcus suis Ga5DH cell shape,cell division FtsZ localization

An unexpected similarity between antibiotic-resistant NDM-1 and beta-lactamaseⅡfrom Erythrobacter litoralis

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Protein & Cell 2011年第3期2卷 250-258页

作者： Beiwen Zheng Shuguang Tan Jia Gao Huiming Han Jun Liu guangwen lu Di Liu Yong Yi Baoli Zhu George F.Gao CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China College of Life Sciences Graduate UniversityChinese Academy of SciencesBeijing 100101China The Key Laboratory of Ministry of Education for Microbial and Plant Genetic Engineering Guangxi UniversityNanning 530004China Network Information Center Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China The 306th Hospital of Chinese PLA China Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100101China

NDM-1(New Delhi metallo-beta-lactamase)gene encodes a metallo-beta-lactamase(MBL)with high carbapenemase activity,which makes the host bacterial strain easily dispatch the last-resort antibiotics known as carbapenems and cause global *** we present the bioinformatics data showing an unexpected similarity between NDM-1 and beta-lactamase II from Erythrobacter litoralis,a marine microbial *** have further expressed these two mature proteins in *** cells,both of which present as a monomer with a molecular mass of 25 *** susceptibility assay reveals that they share similar substrate specificities and are sensitive to aztreonam and *** conformational change accompanied with the zinc binding visualized by nuclear magnetic resonance,Zn2+-bound NDM-1,adopts at least some stable tertiary structure in contrast to the metal-free *** work implies a close evolutionary relationship between antibiotic resistance genes in environmental reservoir and in the clinic,challenging the antimicrobial resistance monitoring.

关键词： NDM-1 metallo-β-lactamase Erythrobacter litoralis similarity antibiotics resistance

hNUDT16:a universal decapping enzyme for small nucleolar RNA and cytoplasmic mRNA

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Protein & Cell 2011年第1期2卷 64-73页

作者： guangwen lu Jie Zhang Yan Li Zhixin Li Na Zhang Xiang Xu Tingting Wang Zhenhong Guan George F.Gao Jinghua Yan CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI) Institute of MicrobiologyChinese Academy of Sciences(CAS)Beijing 100101China Graduate University Chinese Academy of SciencesBeijing 100049China College of Life Science Anhui Agricultural UniversityAnhui 230036China Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100101China

Human NUDT16(hNUDT16)is a decapping enzyme initially identified as the human homolog to the Xenopus laevis *** a metalloenzyme,hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m7 GDP and m227GDP from *** also determines substrate specificity of the *** far,only U8 small nucleolar RNA(snoRNA)has been identified as the substrate of hNUDT16 in the presence of Mg2+.Here we demonstrate that besides U8,hNUDT16 can also actively cleave the m7 GDP cap from mRNAs in the presence of Mg2+or Mn2+.We further show that hNUDT16 does not preferentially recognize U8 or mRNA substrates by our cross-inhibition and quantitative decapping *** addition,our mutagenesis analysis identifies several key residues involved in hydrolysis and confirms the key role of the REXXEE motif in *** an investigation into the subcellular localization of hNUDT16 revealed its abundance in both cytoplasm and *** findings extend the substrate spectrum of hNUDT16 beyond snoRNAs to also include mRNA,demonstrating the pleiotropic decapping activity of hNUDT16.

关键词： hNUDT16 mRNA U8 small nucleolar RNA decapping activity substrate specificity subcellular localization

Crystal structure of SARS-CoV-2 nsp10/nsp162′-O-methylase and its implication on antiviral drug design

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1251-1254页

作者： Sheng Lin Hua Chen Fei Ye Zimin Chen Fanli Yang Yue Zheng Yu Cao Jingxin Qiao Shengyong Yang guangwen lu West China Hospital Emergency Department(WCHED) State Key Laboratory of Biotherapy and Cancer CenterWest China Hospital and Collaborative Innovation Center of BiotherapySichuan University610041 ChengduSichuanChina Disaster Medicine Center West China HospitalSichuan University610041 ChengduSichuanChina

Dear Editor,The unexpected outbreak of a novel human coronavirus infection has imposed great threat to public *** far,this newly-identified virus has spread to 215 countries and territories,infected more than 3.5 million people,and caused over 240,000 deaths worldwide.1 Although intensified countermeasures have been implemented globally to control the virus infection,the pandemic is still surging with a daily increase in infection case of over 65,000 ever since April 1st 2020.1 No prophylactic vaccines or clinical drugs are currently available to prevent or treat the disease,namely coronavirus disease 2019(COVID-19).

关键词： infection drugs intensified

Characterization of SARS-CoV-2 Omicron spike RBD reveals significantly decreased stability, severe evasion of neutralizing- antibody recognition but unaffected engagement by decoy ACE2 modified for enhanced RBD binding

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Signal Transduction and Targeted Therapy 2022年第3期7卷 622-624页

作者： Sheng Lin Zimin Chen Xindan Zhang Ao Wen Xin Yuan Chongzhang Yu Jing Yang Bin He Yu Cao guangwen lu West China Hospital Emergency Department(WCHED) State Key Laboratory of BiotherapyWest Chino HospitalSichuan University610041 ChengduSichuanChina Disaster Medicine Center West China HospitalSichuan University610041 ChengduSichuanChina

Dear Editor,The recent-emerging Omicron variant(B.1.1.529 lineage)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has raised serious public concern because of its rapid regional-and *** of 11th January 2022,the Omicron variant has spread to 140 countries,territories or areas through infected air travelers,and the number is continuously increasing.

关键词： ACE2 decoy RBD