检索结果-内蒙古大学图书馆

Programmable adenine deamination in bacteria using a Cas9-adenine-deaminase fusion

CHEMICAL SCIENCE 2020年第6期11卷 1657-1664页

作者： Zhang, Ya Zhang, Hongyuan Wang, Zhipeng Wu, zhaowei Wang, Yu Tang, Na Xu, Xuexia zhao, suwen Chen, Weizhong Ji, Quanjiang ShanghaiTech Univ Sch Phys Sci & Technol Shanghai 201210 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Jiangxi Agr Univ Coll Life Sci & Engn Nanchang 330045 Jiangxi Peoples R China ShanghaiTech Univ IHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China

Precise genetic manipulation is vital to studying bacterial physiology, but is difficult to achieve in some bacterial species due to the weak intrinsic homologous recombination (HR) capacity and lack of a compatible exogenous HR system. Here we report the establishment of a rapid and efficient method for directly converting adenine to guanine in bacterial genomes using the fusion of an adenine deaminase and a Cas9 nickase. The method achieves the conversion of adenine to guanine via an enzymatic deamination reaction and a subsequent DNA replication process rather than HR, which is utilized in conventional bacterial genetic manipulation methods, thereby substantially simplifying the genome editing process. A systematic screening targeting the possibly editable adenine sites of cntBC, the importer of the staphylopine/metal complex in Staphylococcus aureus, pinpoints key residues for metal importation, demonstrating that application of the system would greatly facilitate the genomic engineering of bacteria.

关键词： Bacteria

来源：评论

学校读者我要写书评

暂无评论

Alternative Z-genome biosynthesis pathway shows evolutionary progression from Archaea to phage

引用

NATURE MICROBIOLOGY 2023年第7期8卷 1330-+页

作者： Tong, Yang Wu, Xinying Liu, Yang Chen, Huiyu Zhou, Yan Jiang, Li Li, Meng zhao, suwen Zhang, Yan Tianjin Univ Sch Pharmaceut Sci & Technol Collaborat Innovat Ctr Chem Sci & Engn Tianjin Key Lab Modern Drug Delivery & High Effici Tianjin Peoples R China Tianjin Univ Minist Educ Frontiers Sci Ctr Synthet Biol Tianjin Peoples R China Tianjin Univ Sch Chem Engn & Technol Minist Educ Key Lab Syst Bioengn Tianjin Peoples R China Tianjin Univ Dept Chem Tianjin Peoples R China ShanghaiTech Univ iHuman Inst Shanghai Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai Peoples R China Shenzhen Univ Inst Adv Study Archaeal Biol Ctr Shenzhen Peoples R China Shenzhen Univ Inst Adv Study Shenzhen Key Lab Marine Microbiome Engn Shenzhen Peoples R China

Many bacteriophages evade bacterial immune recognition by substituting adenine with 2,6-diaminopurine (Z) in their genomes. The Z-genome biosynthetic pathway involves PurZ that belongs to the PurA (adenylosuccinate synthetase) family and bears particular similarity to archaeal PurA. However, how the transition of PurA to PurZ occurred during evolution is not clear;recapturing this process may shed light on the origin of Z-containing phages. Here we describe the computer-guided identification and biochemical characterization of a naturally existing PurZ variant, PurZ0, which uses guanosine triphosphate as the phosphate donor rather than the ATP used by PurZ. The atomic resolution structure of PurZ0 reveals a guanine nucleotide binding pocket highly analogous to that of archaeal PurA. Phylogenetic analyses suggest PurZ0 as an intermediate during the evolution of archaeal PurA to phage PurZ. Maintaining the balance of different purines necessitates further evolvement of guanosine triphosphate-using PurZ0 to ATP-using PurZ in adaptation to Z-genome life. An alternative diaminopurine (Z) biosynthetic pathway using PurZ0 is found in bacteriophages and used for bacterial immune evasion, with higher structural and biochemical similarities to archaeal PurA than PurZ.

关键词：

来源：评论

学校读者我要写书评

暂无评论

A Unique cis-3-Hydroxy-L-proline Dehydratase in the Enolase Superfamily

引用

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2015年第4期137卷 1388-1391页

作者： Zhang, Xinshuai Kumar, Ritesh Vetting, Matthew W. zhao, suwen Jacobson, Matthew P. Almo, Steven C. Gerlt, John A. Univ Illinois Dept Biochem Urbana IL 61801 USA Univ Illinois Dept Chem Urbana IL 61801 USA Univ Illinois Inst Genom Biol Urbana IL 61801 USA Albert Einstein Coll Med Dept Biochem Bronx NY 10461 USA Univ Calif San Francisco Dept Pharmaceut Chem San Francisco CA 94143 USA

The genome of Labrenzia aggregata IAM 12614 encodes an uncharacterized member of the muconate lactonizing enzyme (MLE) subgroup of the enolase superfamily (UniProt ID A0NXQ8). The gene encoding A0NXQ8 is located between genes that encode members of the proline racemase superfamily, 4R-hydroxyproline 2-epimerase (UniProt ID A0NXQ7;4HypE) and trans-3-hydroxy-l-proline dehydratase (UniProt ID A0NXQ9;t3LHypD). A0NXQ8 was screened with a library of proline analogues;two reactions were observed with cis-3-hydroxy-l-proline (c3LHyp), competing 2-epimerization to trans-3-hydroxy-d-proline (1,1-proton transfer) and dehydration to Delta(1)-pyrroline-2-carboxylate (beta-elimination;c3LHyp dehydratase), with eventual total dehydration. The genome context encoding A0NXQ8 both (1) confirms its novel c3LHyp dehydratase function and (2) provides evidence for metabolic pathways that allow L. aggregata to utilize several isomeric 3- and 4-hydroxyprolines as sole carbon sources.

关键词： ENZYMES RESEARCH ENOLASE PROLINE EPIMERASES CARBOXYLATES

来源：评论

学校读者我要写书评

暂无评论

Structure-Based Design of Dual-Acting Compounds Targeting Adenosine A_2A Receptor and Histone Deacetylase as Novel Tumor Immunotherapeutic Agents

引用

JOURNAL OF MEDICINAL CHEMISTRY 2021年第22期64卷 16573-16597页

作者： Yan, Wenzhong Ling, Lijun Wu, Yiran Yang, Kexin Liu, Ruiquan Zhang, Jinfeng zhao, Simeng Zhong, Guisheng zhao, suwen Jiang, Hualiang Xie, Chengying Cheng, Jianjun ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Shanghai Inst Adv Immunochem Studies Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Chinese Acad Sci Shanghai Inst Mat Med State Key Lab Drug Res Drug Discovery & Design Ctr Shanghai 201203 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China

Adenosine is an immunosuppressive factor in the tumor microenvironment mainly through activation of the A(2A) adenosine receptor (A(2A)R), which is a mechanism hijacked by tumors to escape immune surveillance. Small-molecule A(2A)R antagonists are being evaluated in clinical trials as immunotherapeutic agents, but their efficacy is limited as standalone therapies. To enhance the antitumor effects of A(2A)R antagonists, dual-acting compounds incorporating A(2A)R antagonism and histone deacetylase (HDAC) inhibitory actions were designed and synthesized, based on co-crystal structures of A(2A)R. Compound 24e (IHCH-3064) exhibited potent binding to A(2A)R (K-i = 2.2 nM) and selective inhibition of HDAC1 (IC50 = 80.2 nM), with good antiproliferative activity against tumor cell lines in vitro. Intraperitoneal administration of 24e (60 mg/kg, bid) inhibited mouse MC38 tumor growth with a tumor growth inhibition rate of 95.3%. These results showed that dual-acting compounds targeting A(2A)R and HDAC are potentially immunotherapeutic agents that are worth further exploring.

关键词： Hydrocarbons Antagonists Peptides and proteins Inhibition Alkyls

来源：评论

学校读者我要写书评

暂无评论

Furin cleavage sites naturally occur in coronaviruses

引用

STEM CELL RESEARCH 2021年 50卷 102115-102115页

作者： Wu, Yiran zhao, suwen Shanghai Tech Univ iHuman Inst Shanghai 201210 Peoples R China Shanghai Tech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China

The spike protein is a focused target of COVID-19, a pandemic caused by SARS-CoV-2. A 12-nt insertion at S1/S2 in the spike coding sequence yields a furin cleavage site, which raised controversy views on origin of the virus. Here we analyzed the phylogenetic relationships of coronavirus spike proteins and mapped furin recognition motif on the tree. Furin cleavage sites occurred independently for multiple times in the evolution of the coronavirus family, supporting the natural occurring hypothesis of SARS-CoV-2.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Affinity Mass Spectrometry-Based Fragment Screening Identified a New Negative Allosteric Modulator of the Adenosine A2A Receptor Targeting the Sodium Ion Pocket

引用

ACS CHEMICAL BIOLOGY 2021年第6期16卷 991-1002页

作者： Lu, Yan Liu, Hongyue Yang, Dehua Zhong, Li Xin, Ye zhao, suwen Wang, Ming-Wei Zhou, Qingtong Shui, Wenqing ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Chinese Acad Sci Natl Ctr Drug Screening Shanghai Inst Mat Med Shanghai 201203 Peoples R China Chinese Acad Sci CAS Key Lab Receptor Res Shanghai Inst Mat Med Shanghai 201203 Peoples R China Fudan Univ Sch Pharm Shanghai 201203 Peoples R China Fudan Univ Sch Basic Med Sci Shanghai 200032 Peoples R China

Allosteric ligands provide new opportunities to modulate G protein-coupled receptor (GPCR) function and present therapeutic benefits over orthosteric molecules. Negative allosteric modulators (NAMs) can inhibit the activation of a receptor and downstream signal transduction. Screening NAMs for a GPCR target is particularly challenging because of the difficulty in distinguishing NAMs from antagonists bound to the orthosteric site as they both show inhibitory effects in receptor signaling assays. Here we report an affinity mass spectrometry (MS)-based approach tailored to screening potential NAMs of a GPCR target especially from fragment libraries. Compared to regular surface plasmon resonance or NMR-based methods for fragment screening, our approach features a reduction of the protein and compound consumption by 2-4 orders of magnitude and an increase in the data acquisition speed by 2-3 orders of magnitude. Our affinity MS-based fragment screening led to the identification of a new NAM of the adenosine A(2A) receptor (A(2A)AR) bearing an unprecedented azetidine moiety predicted to occupy the allosteric sodium binding site. Molecular dynamics simulations, ligand structure-activity relationship (SAR) studies, and in-solution NMR analyses further revealed the unique binding mode and antagonistic property of this compound that differs considerably from HMA (5-(N,N-hexamethylene)amiloride), a well-characterized NAM of A(2A)AR. Taken together, our work would facilitate fragment-based screening of allosteric modulators, as well as guide the design of novel NAMs acting at the sodium ion pocket of class A GPCRs.

关键词： Ligands Assays Sodium Nicotinamide Receptors

来源：评论

学校读者我要写书评

暂无评论

Design and Synthesis of Bitopic 2-Phenylcyclopropylmethylamine (PCPMA) Derivatives as Selective Dopamine D3 Receptor Ligands

引用

JOURNAL OF MEDICINAL CHEMISTRY 2020年第9期63卷 4579-4602页

作者： Tan, Liang Zhou, Qingtong Yan, Wenzhong Sun, Jian Kozikowski, Alan P. zhao, suwen Huang, Xi-Ping Cheng, Jianjun Univ N Carolina Chapel Hill Med Sch Dept Pharmacol Natl Inst Mental HlthPsychoact Drug Screening Pr Chapel Hill NC 27599 USA ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China StarWise Therapeut LLC Chicago IL 60614 USA ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China

2-Phenylcyclopropylmethylamine (PCPMA) analogues have been reported as selective serotonin 2C agonists. On the basis of the same scaffold, we designed and synthesized a series of bitopic derivatives as dopamine D3R ligands. A number of these new compounds show a high binding affinity for D3R with excellent selectivity. Compound (1R,2R)-22e and its enantiomer (1S,2S)-22e show a comparable binding affinity for the D3R, but the former is a potent D3R agonist, while the latter acts as an antagonist. Molecular docking studies revealed different binding poses of the PCPMA moiety within the orthosteric binding pocket of the D3R, which might explain the different functional profiles of the enantiomers. Compound (1R,2R)-30q shows a high binding affinity for the D3R (K-i = 2.2 nM) along with good selectivity, as well as good bioavailability and brain penetration properties in mice. These results reveal that the PCPMA scaffold may serve as a privileged scaffold for the design of aminergic GPCR ligands.

关键词： Agonists Molecular structure Selectivity Screening assays Receptors

来源：评论

学校读者我要写书评

暂无评论

Molecular Imaging of Collagen Destruction of the Spine

引用

ACS NANO 2021年第12期15卷 19138-19149页

作者： Liu, Lei Huang, Kui Li, Wei Qiu, Rongmao Fang, Yijie Huang, Yongjie zhao, suwen Lv, Hai Zhang, Kuibo Shan, Hong Li, Yang Sun Yat Sen Univ Affiliated Hosp 5 Guangdong Prov Key Lab Biomed Imaging Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Guangdong Prov Engn Res Ctr Mol Imaging Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Dept Spine Surg Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Dept Pathol Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Dept Radiol Zhuhai 519000 Peoples R China Sun Yat Sen Univ Affiliated Hosp 5 Dept Intervent Med Zhuhai 519000 Peoples R China

As the leading cause of disability worldwide, low back pain is commonly caused by biomechanical and catabolic disruptions to key structures of the spine, such as intervertebral discs and facet joints. To date, accurate, noninvasive detection of microdestruction within these tissues remains an elusive goal. Here, we report an in vivo imaging approach based on a collagen hybridizing peptide (CHP) that specifically targets disruption to the extracellular matrix architecture at the molecular scale-the denatured collagen molecules. Utilizing fluorescently labeled CHPs, live animal imaging, and light sheet fluorescence microscopy, we mapped collagen destruction in the lumbar spines in 3D, revealing that under normal conditions collagen destruction was localized to load-bearing anatomical structures including annulus fibrosus of the disc and the facet joints, where aging, tensile force (hindlimb suspension), and disc degeneration (needle puncture) escalated the CHP-binding in specific mouse models. We showed that targeting denatured collagen molecules allowed for an accurate, quantifiable interrogation of the structural integrity of these spinal matrixes with a greater sensitivity than anatomical imaging and histology. Finally, we demonstrated CHP's binding to degenerated human discs, suggesting exciting potentials for applying CHP for diagnosing, monitoring, and treating various spinal disorders, including intervertebral disc degeneration, facet joint osteoarthritis, and ankylosing spondylitis.

关键词： spinal disorder intervertebral disc degeneration facet joint microdestruction collagen triple helix

来源：评论

学校读者我要写书评

暂无评论

The proline synthesis enzyme P5CS forms cytoophidia in Drosophila

引用

Journal of Genetics and Genomics 2020年第3期47卷 131-143页

作者： Bo Zhang Omür Y.Tastan Xian Zhou Chen-Jun Guo Xuyang Liu Aaron Thind Huan-Huan Hu suwen zhao Ji-Long Liu School of Life Science and Technology ShanghaiTech UniversityShanghai201210China Institute of Biochemistry and Cell Biology Shanghai Institutes for Biologicai SciencesChinese Academy of SciencesShanghai200031China University of Chinese Academy of Sciences Beijing100049China MRC Functional Genomics Unit Department of PhysiologyAnatomy and GeneticsUniversity of OxfordOxford0X13PTUnited Kingdom iHuman Institute ShanghaiTech UniversityShanghai201210China

Compartmentation of enzymes via filamentation has arisen as a mechanism for the regulation of *** 2010,three groups independently reported that CTP synthase(CTPS)can assemble into a filamentous structure termed the *** searching for CTPS-interacting proteins,here we perform a yeast two-hybrid screening of Drosophila proteins and identify a putative CTPS-interacting protein,△~1-pyrroline-5-carboxylate synthase(P5CS).Using the Drosophila follicle cell as the in vivo model,we confirm that P5CS forms cytoophidia,which are associated with CTPS *** of P5CS increases the length of CTPS ***,filamentation of CTPS affects the morphology of P5CS cytoophid ***,in vitro analyses confirm the filament-fo rming property of *** work links CTPS with P5CS,two enzymes involved in the rate-limiting steps in pyrimidine and proline biosynthesis,respectively.

关键词： CTPS Cytoophidium Drosophila Glutamate P5CS Proline

来源：评论

学校读者我要写书评

暂无评论

The structure-based traceless specific fluorescence labeling of the smoothened receptor

引用

ORGANIC & BIOMOLECULAR CHEMISTRY 2019年第25期17卷 6136-6142页

作者： Xue, Dongxiang Ye, Lintao Zheng, Jun Wu, Yiran Zhang, Xianjun Xu, Yueming Li, Tao Stevens, Raymond C. Xu, Fei Zhuang, Min zhao, suwen zhao, Fei Tao, Houchao ShanghaiTech Univ iHuman Inst Ren Bldg393 Middle Huaxia Rd Shanghai 201210 Peoples R China Chinese Acad Sci Shanghai Inst Mat Med 555 Zuchongzhi RdBldg 3Room 426 Shanghai 201203 Peoples R China Univ Chinese Acad Sci 19A Yuquan Rd Beijing 100049 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China

The smoothened receptor (SMO) mediates the hedgehog (Hh) signaling pathway and plays a vital role in embryonic development and tumorigenesis. The visualization of SMO has the potential to provide new insights into its enigmatic mechanisms and associated disease pathogenesis. Based on recent progress in structural studies of SMO, we have designed and characterized a group of affinity probes to facilitate the turn-on fluorescence labeling of SMO at the epsilon-amine of K395. These chemical probes were derived from a potent SMO antagonist skeleton by the conjugation of a small non-fluorescent unit, O-nitrobenzoxadiazole (O-NBD). In this context, optimal probes were developed to be capable of efficiently and selectively lighting up SMO regardless of whether it is in micelles or in native membranes. More importantly, the resulting labeled SMO only bears a very small fluorophore and allows for the recovery of the unoccupied pocket by dissociation of the residual ligand module. These advantages should allow the probe to serve as a potential tool for monitoring SMO trafficking, understanding Hh activation mechanisms, and even the diagnosis of tumorigenesis in the future.

关键词： Probes

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：