检索结果-内蒙古大学图书馆

Association analysis between novel variants in LEPR gene and litter size in Mongolia and ujimqin sheep breeds

THERIOGENOLOGY 2022年 183卷 79-89页

作者： Ma, Shujiao Ji, Xuewen Cang, Ming Wang, Jianguo Yu, Haiquan Liu, Yongbin Zhang, Wenguang Wu, Yiran zhao, suwen Cao, Guifang Tong, Bin Inner Mongolia Univ Sch Life Sci State Key Lab Reprod Regulat & Breeding Grassland Hohhot Peoples R China Inner Mongolia Acad Agr & Anim Husb Sci Inst Anim Sci Hohhot Peoples R China Inner Mongolia Agr Univ Coll Anim Sci Hohhot Peoples R China ShanghaiTech Univ Sch Life Sci & Technol iHuman Inst Shanghai Peoples R China Inner Mongolia Agr Univ Dept Vet Hohhot Peoples R China

Prolificacy is an important trait of livestock, especially for species with multiple births, such as sheep. The leptin receptor (LEPR) is considered as a major candidate gene that affects the reproductive traits of sheep. The known R62H mutation in the LEPR gene is associated with the hyperprolific phenotype of Davisdale sheep. However, studies identifying novel variations and seeking breed-specific markers associated with litter size in other sheep breeds are rare. In this study, we sequenced all coding regions of the LEPR gene of Mongolia sheep, and nine novel variants of the LEPR gene were detected by direct sequencing. Among them, the synonymous c.240C > T and c.279C > T mutations were significantly associated with the litter sizes of Mongolia ewes (P < 0.05 and P < 0.01, respectively) and Ujimqin ewes (P < 0.05 and P < 0.01, respectively). The silent c.240C > T and c.279C > T mutations are predicted to change the stability of the mRNA secondary structure by reducing the minimum free energy and are predicted to change the mRNA secondary structure of LEPR. Our findings may provide potentially useful genetic markers for increasing litter size in sheep. (c) 2022 Elsevier Inc. All rights reserved.

关键词： Association LEPR Litter size Novel mutation Mongolia sheep Ujimqin sheep

来源：评论

学校读者我要写书评

暂无评论

Transition-Linker Containing Detergents for Membrane Protein Studies

引用

CHEMISTRY-A EUROPEAN JOURNAL 2022年第69期28卷 e202202242-e202202242页

作者： Luo, Weiling Yang, Meifang zhao, Yitian Wang, Huixia Yang, Xiaodi Zhang, Wei zhao, Fei zhao, suwen Tao, Houchao Shanghai Univ Tradit Chinese Med Shanghai Frontiers Sci Ctr TCM Chem Biol Innovat Res Inst Tradit Chinese Med Shanghai 201203 Peoples R China ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Hebei Normal Univ Coll Chem & Mat Sci Shijiazhuang 050024 Hebei Peoples R China

It is a pressing need, but still challenging to explore the structure and function of membrane proteins (MPs). One of the main obstacles is the limited availability of matched detergents for the handling of specific MPs. We describe herein the design of new detergents by incorporation of a transition linker between the hydrophilic head and the hydrophobic tail. This design allows a gradual change of hydrophobicity between the outside and inside of micelles, in contrast to the abrupt switch in conventional detergents. Notably, many of these detergents assembled into micelles in while retaining low critical micelle concentrations. Meanwhile, thermal stabilizing evaluation identified superior detergents for representative MPs, including G protein-coupled receptors and a transporter protein. Among them, further improved the NMR study of MPs. We anticipate these that results will encourage future detergent expansion through new remodeling on the traditional detergent scaffold.

关键词： detergents membrane proteins micelles NMR spectroscopy transition linkers

来源：评论

学校读者我要写书评

暂无评论

Inactivity of YGL082W in vitro due to impairment of conformational change in the catalytic center loop

引用

Science China Chemistry 2020年第2期63卷 237-243页

作者： Lining Lu Yu Guo Tian Wang Lujun Liang suwen zhao Feng Wang Lei Liu Tsinghua-Peking Center for Life Sciences Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology(Ministry of Education)Center for Synthetic and Systems BiologyState Key Laboratory of Chemical Oncogenomics(Shenzhen)Department of ChemistryTsinghua UniversityBeijing 100084China School of Life Science Beijing Institute of TechnologyBeijing 100081China iHuman Institute School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China

MINDY-1 is a recently discovered new family of deubiquitinating enzymes(DUB),but one of its yeast homologs,YGL082 W,does not show any DUB activity in *** alignment shows that YGL082 W possesses the correct catalytic triad,and yet did not catalyze either the hydrolysis of di-ubiquitin,crosslinking with C-terminally propargylated ubiquitin,or hydrolysis of *** obtaining a crystal structure of the catalytic domain of YGL082 W,we identified an interesting difference between the catalytic center loop of YGL082 W and that of its human homolog *** the conformation of the catalytic center loop was previously reported to be important for the deubiquitination activity of MINDY-1,we hypothesized that Glu27(instead of the corresponding Pro136 in MINDY-1) of the catalytic center loop of YGL082 W may impair the conformational change and account for the lack of *** hypothesis was supported by homology modeling and molecular dynamics simulations,which showed that the Pro-to-Glu mutation(P136 E mutation for MINDY-1) creates a hydrogen bond that inhibits the conformation change of the catalytic center loop of *** experiments through site-directed mutation validated this hypothesis,showing that the P27 E mutation caused MIY1(a homologous active DUB from yeast) to lose activity.

关键词： deubiquitinating enzymes(DUB) enzymology X-ray crystal structure molecular dynamics

来源：评论

学校读者我要写书评

暂无评论

Orthogonally Engineered Albumin with Attenuated Macrophage Phagocytosis for the Targeted Visualization and Phototherapy of Liver Cancer

引用

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2023年第31期145卷 17377-17388页

作者： Dou, Wei-Tao Qiu, Peng Shi, Yuanyuan Zhu, Ling Guo, Chen Li, Na Zang, Yi Liu, Tingting zhao, suwen Pan, Yufei Dong, Liwei Sessler, Jonathan L. Tan, Yexiong Li, Jia Wang, Hongyang Tian, He He, Xiao-Peng East China Univ Sci & Technol Frontiers Ctr Materiobiol & Dynam Chem Sch Chem & Mol Engn Key Lab Adv Mat Shanghai 200237 Peoples R China East China Univ Sci & Technol Frontiers Ctr Materiobiol & Dynam Chem Sch Chem & Mol Engn Joint Int Res Lab Precis Chem & Mol Engn Shanghai 200237 Peoples R China East China Univ Sci & Technol Joint Res Ctr Frontiers Ctr Materiobiol & Dynam Chem Sch Chem & Mol Engn Shanghai 200237 Peoples R China Second Mil Med Univ Eastern Hepatobiliary Surg Inst Natl Ctr Liver Canc Int Cooperat Lab Signal Transduct Shanghai 200433 Peoples R China Chinese Acad Sci Shanghai Adv Res Inst Natl Facil Prot Sci Shanghai Shanghai 201210 Peoples R China Chinese Acad Sci Shanghai Inst Mat Med Natl Ctr Drug Screening Shanghai 201203 Peoples R China Lingang Lab Shanghai 201203 Peoples R China ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China Univ Texas Austin Dept Chem Austin TX 78712 USA

The five-year survival rate of hepatocellular carcinoma(HCC) remainsunsatisfactory. This reflects, in part, the paucity of effective methodsthat allow the target-specific diagnosis and therapy of HCC. Here,we report a strategy based on engineered human serum albumin (HSA)that permits the HCC-targeted delivery of diagnostic and therapeuticagents. Covalent cysteine conjugation combined with the exploitationof host-guest chemistry was used to effect the orthogonal functionalizationof HSA with two functionally independent peptides. One of these peptidestargets glypican-3 (GPC-3), an HCC-specific biomarker, while the secondreduces macrophage phagocytosis through immune-checkpoint *** orthogonally engineered HSA proved effective for the GPC-3-targeteddelivery of near-infrared fluorescent and phototherapeutic agents,thus permitting target-specific optical visualization and photodynamicablation of HCC in vivo. This study thus offers new insights intospecificity-enhanced fluorescence-guided surgery and phototherapyof HCC through the orthogonal engineering of biocompatible proteins.

关键词： Cancer Cells Fluorescence Immunology Peptides and proteins

来源：评论

学校读者我要写书评

暂无评论

The versatile binding landscape of the TAAR1 pocket for LSD and other antipsychotic drug molecules

引用

CELL REPORTS 2024年第7期43卷 114505页

作者： Jiang, Kexin Zheng, You Zeng, Liting Wang, Ling Li, Fei Pu, Jun Lu, Yingli zhao, suwen Xu, Fei ShanghaiTech Univ iHuman Inst Shanghai Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai Peoples R China Kunming Med Univ Dept Neurosurg Affiliated Hosp 2 Kunming Peoples R China Shanghai Jiao Tong Univ Shanghai Peoples Hosp 9 Inst & Dept Endocrinol & Metab Sch Med Shanghai Peoples R China Shanghai Clin Res & Trial Ctr Shanghai Peoples R China

Increasing global concerns about psychoactive substance addiction and psychotic disorders highlight the need for comprehensive research into the structure-function relationship governing ligand recognition between these substances and their receptors in the brain. Recent studies indicate the significant involvement of trace amine-associated receptor 1 (TAAR1) in the signaling regulation of the hallucinogen lysergic acid diethylamide (LSD) and other antipsychotic drugs. This study presents structures of the TAAR1-Gs protein complex recognizing LSD, which exhibits a polypharmacological profile, and the partial agonist RO5263397, which is a drug candidate for schizophrenia and addiction. Moreover, we elucidate the cross-species recognition and partial activation mechanism for TAAR1, which holds promising implications from a drug discovery perspective. Through mutagenesis, functional studies, and molecular dynamics (MD) simulations, we provide a comprehensive understanding of a versatile TAAR1 pocket in recognizing various ligands as well as in the ligand-free state, underpinning the structural basis of its high adaptability. These findings offer valuable insights for the design of antipsychotic drugs.

关键词： CP: Neuroscience

来源：评论

学校读者我要写书评

暂无评论

Development of Yin-Yang ligand for cannabinoid receptors

引用

BIOORGANIC CHEMISTRY 2023年第1期133卷 106377页

作者： Qiu, Yanli zhao, Yitian Hu, Tao Yang, Meifang Li, Fei Li, Cuixia Gu, Weiliang Yang, Xiaodi zhao, suwen Tao, Houchao Shanghai Univ Tradit Chinese Med Innovat Res Inst Tradit Chinese Med Shanghai Frontiers Sci Ctr TCM Chem Biol Shanghai 201203 Peoples R China ShanghaiTech Univ iHuman Inst Shanghai 201210 Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai 201210 Peoples R China Shanghai Univ Tradit Chinese Med Sch Pharm Dept Pharmacol Shanghai 201203 Peoples R China Shanghai Univ Tradit Chinese Med Shanghai 201203 Peoples R China ShanghaiTech Univ Shanghai 201210 Peoples R China

Cannabinoid receptors (CBs), including CB1 and CB2, are the key components of a lipid signaling endocannabinoid system (ECS). Development of synthetic cannabinoids has been attractive to modulate ECS functions. CB1 and CB2 are structurally closely related subtypes but with distinct functions. While most efforts focus on the development of selective ligands for single subtype to circumvent the undesired off-target effect, Yin-Yang ligands with opposite pharmacological activities simultaneously on two subtypes, offer unique therapeutic potential. Herein we report the development of a new Yin-Yang ligand which functions as an antagonist for CB1 and concurrently an agonist for CB2. We found that in the pyrazole-cored scaffold, the arm of N1-phenyl group could be a switch, modification of which yielded various ligands with distinct activities. As such, the ortho-morpholine substitution exerted the desired Yin-Yang bifunctionality which, based on the docking study and molecular dynamic simulation, was proposed to be resulted from the hydrogen bonding with S173 and S285 in CB1 and CB2, respectively. Our results demonstrated the feasibility of structure guided ligand evolution for challenging Yin-Yang ligand.

关键词： Cannabinoid receptors Docking and simulation Drug design Subtype selectivity Yin -Yang ligand

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

Zero-shot prediction of mutation effects with multimodal deep representation learning guides protein engineering

引用

CELL RESEARCH 2024年第9期34卷 630-647页

作者： Cheng, Peng Mao, Cong Tang, Jin Yang, Sen Cheng, Yu Wang, Wuke Gu, Qiuxi Han, Wei Chen, Hao Li, Sihan Chen, Yaofeng Zhou, Jianglin Li, Wuju Pan, Aimin zhao, suwen Huang, Xingxu Zhu, Shiqiang Zhang, Jun Shu, Wenjie Wang, Shengqi Bioinformat Ctr AMMS Beijing Peoples R China Nanjing Med Univ Womens Hosp Nanjing Matern & Child Hlth Care Hosp State Key Lab Reprod Med & Offspring Hlth Nanjing Jiangsu Peoples R China Zhejiang Lab Hangzhou Zhejiang Peoples R China ShanghaiTech Univ IHuman Inst Shanghai Peoples R China ShanghaiTech Univ Sch Life Sci & Technol Shanghai Peoples R China

Mutations in amino acid sequences can provoke changes in protein function. Accurate and unsupervised prediction of mutation effects is critical in biotechnology and biomedicine, but remains a fundamental challenge. To resolve this challenge, here we present Protein Mutational Effect Predictor (ProMEP), a general and multiple sequence alignment-free method that enables zero-shot prediction of mutation effects. A multimodal deep representation learning model embedded in ProMEP was developed to comprehensively learn both sequence and structure contexts from similar to 160 million proteins. ProMEP achieves state-of-the-art performance in mutational effect prediction and accomplishes a tremendous improvement in speed, enabling efficient and intelligent protein engineering. Specifically, ProMEP accurately forecasts mutational consequences on the gene-editing enzymes TnpB and TadA, and successfully guides the development of high-performance gene-editing tools with their engineered variants. The gene-editing efficiency of a 5-site mutant of TnpB reaches up to 74.04% (vs 24.66% for the wild type);and the base editing tool developed on the basis of a TadA 15-site mutant (in addition to the A106V/D108N double mutation that renders deoxyadenosine deaminase activity to TadA) exhibits an A-to-G conversion frequency of up to 77.27% (vs 69.80% for ABE8e, a previous TadA-based adenine base editor) with significantly reduced bystander and off-target effects compared to ABE8e. ProMEP not only showcases superior performance in predicting mutational effects on proteins but also demonstrates a great capability to guide protein engineering. Therefore, ProMEP enables efficient exploration of the gigantic protein space and facilitates practical design of proteins, thereby advancing studies in biomedicine and synthetic biology.

关键词：

来源：评论

学校读者我要写书评

暂无评论

A core epitope targeting antibody of SARS-CoV-2

引用

Protein & Cell 2023年第1期14卷 74-78页

作者： Simeng zhao Fengjiang Liu Shizhen Qiu Qiaoshuai Lan Yiran Wu Wei Xu Junzi Ke Jie Yang Xiaoyan Liu Kun Wang Hangtian Guo Shuai Xia Fangfang Zhang Jiabei Wang Xiaowen Hu Lu Lu Shibo Jiang suwen zhao Lianxin Liu Youhua Xie Xiuna Yang Haopeng Wang Guisheng Zhong iHuman Institute ShanghaiTech UniversityShanghai 201210China Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech UniversityShanghai 201210China Innovative Center for Pathogen Research Guangzhou LaboratoryGuangzhou 510005China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical Sciences and Biosafety Level 3 LaboratoryFudan UniversityShanghai 200032China Department of Hepatobiliary Surgery Anhui Province Key Laboratory of Hepatopancreatobiliary SurgeryThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineThe University of Science and Technology of ChinaHefei 230001China Department of Pulmonary and Critical Care Medicine Division of Life Sciences and MedicineThe First Affiliated Hospital of USTCThe University of Science and Technology of ChinaHefei 230026China Division of Life Sciences and Medicine The First Affiliated Hospital of USTCThe University of Sciences and Technology of ChinaHefei 230001China

Dear Editor,Tremendous efforts have been made globally to develop therapeutics and prophylactics against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)which has caused thousands of millions of infections and deaths worldwide.A series of potent neutralizing antibodies with defined epitopes targeting RBD have been recently identified with different ***,being an RNA virus,the instability of the SARS-CoV-2 genome results in numerous S-protein variants with altered viral phenotypes.

关键词： acute respiratory globally

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

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：