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118 results on '"Yuan, Yanqiu"'

1. Tumor mitochondrial oxidative phosphorylation stimulated by the nuclear receptor RORγ represents an effective therapeutic opportunity in osteosarcoma.

Author

Zheng, Jianwei, Wang, Qianqian, Chen, Jianghe, Cai, Guodi, Zhang, Zhenhua, Zou, Hongye, Zou, June, Liu, Qianqian, Ji, Shufeng, Shao, Guoli, Li, Hong, Li, Sheng, Chen, Hongwu, Lu, LinLin, Yuan, Yanqiu, Liu, Peiqing, and Wang, Junjian

Subjects
Osteosarcoma, Humans, Oxidative Phosphorylation, Mitochondria, Nuclear Receptor Subfamily 1, Group F, Member 3, Cell Line, Tumor, Animals, Bone Neoplasms, Mice, Reactive Oxygen Species, Apoptosis, Gene Expression Regulation, Neoplastic, Ferroptosis, Mice, Nude, Male, Cell Proliferation, RNA-Binding Proteins
Abstract

Osteosarcoma (OS) is the most common malignant bone tumor with a poor prognosis. Here, we show that the nuclear receptor RORγ may serve as a potential therapeutic target in OS. OS exhibits a hyperactivated oxidative phosphorylation (OXPHOS) program, which fuels the carbon source to promote tumor progression. We found that RORγ is overexpressed in OS tumors and is linked to hyperactivated OXPHOS. RORγ induces the expression of PGC-1β and physically interacts with it to activate the OXPHOS program by upregulating the expression of respiratory chain component genes. Inhibition of RORγ strongly inhibits OXPHOS activation, downregulates mitochondrial functions, and increases ROS production, which results in OS cell apoptosis and ferroptosis. RORγ inverse agonists strongly suppressed OS tumor growth and progression and sensitized OS tumors to chemotherapy. Taken together, our results indicate that RORγ is a critical regulator of the OXPHOS program in OS and provides an effective therapeutic strategy for this deadly disease.

Published
2024

8. ETD-Based Proteomic Profiling Improves Arginine Methylation Identification and Reveals Novel PRMT5 Substrates

Author

Lu, Lingzi, Ye, Zilu, Zhang, Rou, Olsen, Jesper V., Yuan, Yanqiu, Mao, Yang, Lu, Lingzi, Ye, Zilu, Zhang, Rou, Olsen, Jesper V., Yuan, Yanqiu, and Mao, Yang

Abstract

Protein arginine methylations are important post-translational modifications (PTMs) in eukaryotes, regulating many biological processes. However, traditional collision-based mass spectrometry methods inevitably cause neutral losses of methylarginines, preventing the deep mining of biologically important sites. Herein we developed an optimized mass spectrometry workflow based on electron-transfer dissociation (ETD) with supplemental activation for proteomic profiling of arginine methylation in human cells. Using symmetric dimethylarginine (sDMA) as an example, we show that the ETD-based optimized workflow significantly improved the identification and site localization of sDMA. Quantitative proteomics identified 138 novel sDMA sites as potential PRMT5 substrates in HeLa cells. Further biochemical studies on SERBP1, a newly identified PRMT5 substrate, confirmed the coexistence of sDMA and asymmetric dimethylarginine in the central RGG/RG motif, and loss of either methylation caused increased the recruitment of SERBP1 to stress granules under oxidative stress. Overall, our optimized workflow not only enabled the identification and localization of extensive, nonoverlapping sDMA sites in human cells but also revealed novel PRMT5 substrates whose sDMA may play potentially important biological functions., Protein arginine methylations are important post-translational modifications (PTMs) in eukaryotes, regulating many biological processes. However, traditional collision-based mass spectrometry methods inevitably cause neutral losses of methylarginines, preventing the deep mining of biologically important sites. Herein we developed an optimized mass spectrometry workflow based on electron-transfer dissociation (ETD) with supplemental activation for proteomic profiling of arginine methylation in human cells. Using symmetric dimethylarginine (sDMA) as an example, we show that the ETD-based optimized workflow significantly improved the identification and site localization of sDMA. Quantitative proteomics identified 138 novel sDMA sites as potential PRMT5 substrates in HeLa cells. Further biochemical studies on SERBP1, a newly identified PRMT5 substrate, confirmed the coexistence of sDMA and asymmetric dimethylarginine in the central RGG/RG motif, and loss of either methylation caused increased the recruitment of SERBP1 to stress granules under oxidative stress. Overall, our optimized workflow not only enabled the identification and localization of extensive, nonoverlapping sDMA sites in human cells but also revealed novel PRMT5 substrates whose sDMA may play potentially important biological functions.

Published
2024

9. Evolving roles of glycosylation in the tug-of-war between virus and host.

Author

Zhai, Xiaofeng, Yuan, Yanqiu, He, Wan-Ting, Wu, Ying, Shi, Yi, Su, Shuo, Du, Quansheng, and Mao, Yang

Subjects
*GLYCANS, *NEURAMINIDASE, *SARS-CoV-2, *GLYCOSYLATION, *CELL receptors
Abstract

This article explores the role of glycans in the interaction between viruses and host cells. It explains how glycans, which are biomolecules found on the surface of both viruses and host cells, are crucial in viral infection and host defense. The article discusses how host cell surface glycans help viruses bind and enter cells, while the immune system recognizes viral surface glycans and targets them for destruction. It also highlights how viruses can manipulate host cell glycans to evade immune detection. The understanding of these mechanisms could contribute to the development of antiviral therapies and vaccines. The article also addresses the challenges and future directions in this area of research. [Extracted from the article]

Published
2024
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11. O-GlcNAcylation stabilizes the autophagy-initiating kinase ULK1 by inhibiting chaperone-mediated autophagy upon HPV infection

Author

Shi, Yingxin, primary, Yan, Sheng, additional, Shao, Guang-Can, additional, Wang, Jinglong, additional, Jian, Yong-Ping, additional, Liu, Bo, additional, Yuan, Yanqiu, additional, Qin, Ke, additional, Nai, Shanshan, additional, Huang, Xiahe, additional, Wang, Yingchun, additional, Chen, Zhenghui, additional, Chen, Xing, additional, Dong, Meng-Qiu, additional, Geng, Yiqun, additional, Xu, Zhi-Xiang, additional, and Li, Jing, additional

Published
2022
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14. Discovery of Novel Antibiotics as Covalent Inhibitors of Fatty Acid Synthesis

Author

Xiaoping Ye, Xiaohan Yang, Shengjun Wang, Yuan Yanqiu, Jia Wang, Meena Sachdeva, Jieyu Tang, Yu Qian, Cai Youyan, Jennifer A. Leeds, and Wenhao Hu

Subjects
Methicillin-Resistant Staphylococcus aureus, 0301 basic medicine, medicine.drug_class, Antibiotics, Microbial Sensitivity Tests, medicine.disease_cause, 01 natural sciences, Biochemistry, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase, Oxazines, Fatty Acid Synthase, Type II, medicine, Structure–activity relationship, Enzyme Inhibitors, Fatty acid synthesis, chemistry.chemical_classification, Molecular Structure, biology, 010405 organic chemistry, General Medicine, biology.organism_classification, Anti-Bacterial Agents, 0104 chemical sciences, 030104 developmental biology, Enzyme, chemistry, Mechanism of action, Staphylococcus aureus, Drug Design, Molecular Medicine, medicine.symptom, Antibacterial activity, Bacteria
Abstract

The steady increase in the prevalence of multidrug-resistant Staphylococcus aureus has made the search for novel antibiotics to combat this clinically important pathogen an urgent matter. In an effort to discover antibacterials with new chemical structures and mechanisms, we performed a growth inhibition screen of a synthetic library against S. aureus and discovered a promising scaffold with a 1,3,5-oxadiazin-2-one core. These compounds are potent against both methicillin-sensitive and methicillin-resistant S. aureus strains. Isolation of compound-resistant strains followed by whole genome sequencing revealed its cellular target as FabH, a key enzyme in bacterial fatty acid synthesis. Detailed mechanism of action studies suggested the compounds inhibit FabH activity by covalently modifying its active site cysteine residue with high selectivity. A crystal structure of FabH protein modified by a selected compound Oxa1 further confirmed covalency and suggested a possible mechanism for reaction. Moreover, the structural snapshot provided an explanation for compound selectivity. On the basis of the structure, we designed and synthesized Oxa1 derivatives and evaluated their antibacterial activity. The structure-activity relationship supports the hypothesis that noncovalent recognition between compounds and FabH is critical for the activity of these covalent inhibitors. We believe further optimization of the current scaffold could lead to an antibacterial with potential to treat drug-resistant bacteria in the clinic.

Published
2020

17. Rorγ Targeting Promotes Apoptosis and Ferroptosis in Osteosarcoma by Reprogramming Mitochondrial Oxidative Phosphorylation

Author

Zheng, Jianwei, primary, Chen, Jianhe, additional, Wang, Qianqian, additional, Cai, Guodi, additional, Zhang, Zhenhua, additional, Zou, Hongye, additional, Chen, Peng, additional, Wang, Haibin, additional, Ji, Shufeng, additional, Shao, Guoli, additional, Chen, Hong-Wu, additional, Lu, LinLin, additional, Yuan, Yanqiu, additional, Liu, Peiqing, additional, and Wang, Junjian, additional

Published
2022
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19. Zinc-Catalyzed Alkyne-Carbonyl Metathesis of Ynamides with Isatins: Stereoselective Access to Fully Substituted Alkenes

Author

Yuan Yanqiu, Chaoqun Ao, Dan Zhang, Shikun Jia, Xiaohan Yang, Wenhao Hu, and Xinfang Xu

Subjects
chemistry.chemical_classification, 010405 organic chemistry, Organic Chemistry, Intermolecular force, chemistry.chemical_element, Alkyne, Zinc, 010402 general chemistry, Metathesis, 01 natural sciences, Combinatorial chemistry, 0104 chemical sciences, Catalysis, chemistry.chemical_compound, chemistry, Amide, Salt metathesis reaction, Stereoselectivity
Abstract

A zinc-catalyzed intermolecular alkyne-carbonyl metathesis reaction of ynamides with isatins followed by an amide to ester conversion has been developed, which produces the indolone derivatives with a fully substituted alkene species in good to high yields. The salient features of this reaction include the following: mild reaction conditions, an inexpensive zinc catalyst, a broad substrate scope, the excellent regiocontrol and stereoselectivity, and amenable to the gram scale.

Published
2019

30. “Addition” and “Subtraction”: Selectivity Design for Type II Maternal Embryonic Leucine Zipper Kinase Inhibitors

Author

Chen, Xin, primary, Giraldes, John, additional, Sprague, Elizabeth R., additional, Shakya, Subarna, additional, Chen, Zhuoliang, additional, Wang, Yaping, additional, Joud, Carol, additional, Mathieu, Simon, additional, Chen, Christine Hiu-Tung, additional, Straub, Christopher, additional, Duca, Jose, additional, Hurov, Kristen, additional, Yuan, Yanqiu, additional, Shao, Wenlin, additional, and Touré, B. Barry, additional

Published
2017
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31. Mitochondrial MOF Regulates Energy Metabolism in Heart Failure via ATP5B Hyperacetylation

Author

Hu, Yuehuai, Zheng, Yongjia, Liu, Cui, You, Yuyu, Wu, Ying, Wang, Panxia, Wu, Yiyang, Ba, Hongjun, Lu, Jing, Yuan, Yanqiu, Liu, Peiqing, and Mao, Yang

Abstract

Lysine acetylation is a conserved post-translational modification involved in energy metabolism in mitochondria and heart function. This study investigates the role of mitochondria-localized lysine acetyltransferase MOF in heart failure (HF). We find that MOF is upregulated in mitochondria during HF and overexpression of mitochondria-targeted MOF (mtMOF) in mouse models results in mitochondria dysfunction, cardiac remodeling and heart failure. Furthermore, SIRT3 knockout aggravates mtMOF-induced damages, underscoring the role of MOF-catalyzed hyperacetylation in HF. Quantitative lysine acetylome analysis identifies ATP5B as a substrate of MOF. We demonstrate that the acetylation of ATP5B at K201, co-regulated by MOF and SIRT3, impairs mitochondrial respiration and energy metabolism both in vitro and in vivo. These findings suggest that the role of MOF in HF could be attributed to its regulation of ATP5B acetylation. Overall, our results highlight the disruptive impact of mitochondrial MOF on cardiac function and emphasize the significance of enzyme-catalyzed acetylation in mitochondria.

Published
2024
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32. Functional and Structural Analysis of a Key Region of the Cell Wall Inhibitor Moenomycin

Author

Fuse, Shinichiro, Tsukamoto, Hirokazu, Yuan, Yanqiu, Wang, Tsung-Shing Andrew, Zhang, Yi, Bolla, Megan, Walker, Suzanne, Sliz, Piotr, and Kahne, Daniel

Abstract

Moenomycin A (MmA) belongs to a family of natural products that inhibit peptidoglycan biosynthesis by binding to the peptidoglycan glycosyltransferases, the enzymes that make the glycan chains of peptidoglycan. MmA is remarkably potent, but its clinical utility has been hampered by poor physicochemical properties. Moenomycin contains three structurally distinct regions: a pentasaccharide, a phosphoglycerate, and a C25 isoprenyl (moenocinyl) lipid tail that gives the molecule its name. The phosphoglycerate moiety links the pentasaccharide to the moenocinyl chain. This moiety contains two negatively charged groups, a phosphoryl group and a carboxylate. Both the phosphoryl group and the carboxylate have previously been implicated in target binding but the role of the carboxylate has not been explored in detail. Here we report the synthesis of six MmA analogues designed to probe the importance of the phosphoglycerate. These analogues were evaluated for antibacterial and enzyme inhibitory activity; the specific contacts between the phosphoglycerate and the protein target were assessed by X-ray crystallography in conjunction with molecular modeling. Both the phosphoryl group and the carboxylate of the phosphoglycerate chain play roles in target binding. The negative charge of the carboxylate, and not its specific structure, appears to be the critical feature in binding since replacing it with a negatively charged acylsulfonamide group produces a more active compound than replacing it with the isosteric amide. Analysis of the ligand−protein contacts suggests that the carboxylate makes a critical contact with an invariant lysine in the active site. The reported work provides information and validated computational methods critical for the design of analogues based on moenomycin scaffolds.

Published
2024
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33. Toward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight

Author

Toure, B. Barry, Giraldes, John, Smith, Troy, Sprague, Elizabeth R., Wang, Yaping, Mathieu, Simon, Chen, Zhuoliang, Mishina, Yuji, Feng, Yun, Yan-Neale, Yan, Shakya, Subarna, Chen, Dongshu, Meyer, Matthew, Puleo, David, Brazell, J. Tres, Straub, Christopher, Sage, David, Wright, Kirk, Yuan, Yanqiu, Chen, Xin, Duca, Jose, Kim, Sean, Tian, Li, Martin, Eric, Hurov, Kristen, Shao, Wenlin, Toure, B. Barry, Giraldes, John, Smith, Troy, Sprague, Elizabeth R., Wang, Yaping, Mathieu, Simon, Chen, Zhuoliang, Mishina, Yuji, Feng, Yun, Yan-Neale, Yan, Shakya, Subarna, Chen, Dongshu, Meyer, Matthew, Puleo, David, Brazell, J. Tres, Straub, Christopher, Sage, David, Wright, Kirk, Yuan, Yanqiu, Chen, Xin, Duca, Jose, Kim, Sean, Tian, Li, Martin, Eric, Hurov, Kristen, and Shao, Wenlin

Abstract

MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the cellular effects observed by short hairpin ribonucleic acid (shRNA)-mediated MELK knockdown in cellular models. We also discovered a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacological inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation., MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the cellular effects observed by short hairpin ribonucleic acid (shRNA)-mediated MELK knockdown in cellular models. We also discovered a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacological inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation.

Published
2016

34. Toward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight

Author

Touré, B. Barry, primary, Giraldes, John, additional, Smith, Troy, additional, Sprague, Elizabeth R., additional, Wang, Yaping, additional, Mathieu, Simon, additional, Chen, Zhuoliang, additional, Mishina, Yuji, additional, Feng, Yun, additional, Yan-Neale, Yan, additional, Shakya, Subarna, additional, Chen, Dongshu, additional, Meyer, Matthew, additional, Puleo, David, additional, Brazell, J. Tres, additional, Straub, Christopher, additional, Sage, David, additional, Wright, Kirk, additional, Yuan, Yanqiu, additional, Chen, Xin, additional, Duca, Jose, additional, Kim, Sean, additional, Tian, Li, additional, Martin, Eric, additional, Hurov, Kristen, additional, and Shao, Wenlin, additional

Published
2016
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35. Yuan, Yanqiu

Author

Yuan, Yanqiu and Yuan, Yanqiu

Published
2014

47. Deletion of the β-Acetoacetyl Synthase FabY in Pseudomonas aeruginosaInduces Hypoacylation of Lipopolysaccharide and Increases Antimicrobial Susceptibility

Author

Six, David A., Yuan, Yanqiu, Leeds, Jennifer A., and Meredith, Timothy C.

Abstract

ABSTRACTThe β-acetoacetyl-acyl carrier protein synthase FabY is a key enzyme in the initiation of fatty acid biosynthesis in Pseudomonas aeruginosa. Deletion of fabYresults in an increased susceptibility of P. aeruginosain vitroto a number of antibiotics, including vancomycin and cephalosporins. Because antibiotic susceptibility can be influenced by changes in membrane lipid composition, we determined the total fatty acid profile of the ΔfabYmutant, which suggested alterations in the lipid A region of the lipopolysaccharide. The majority of lipid A species in the ΔfabYmutant lacked a single secondary lauroyl group, resulting in hypoacylated lipid A. Adding exogenous fatty acids to the growth media restored the wild-type antibiotic susceptibility profile and the wild-type lipid A fatty acid profile. We suggest that incorporation of hypoacylated lipid A species into the outer membrane contributes to the shift in the antibiotic susceptibility profile of the ΔfabYmutant.

Published
2013
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48. In VitroReconstitution of Two Essential Steps in Wall Teichoic Acid Biosynthesis

Author

Ginsberg, Cynthia, Zhang, Yu-Hui, Yuan, Yanqiu, and Walker, Suzanne

Abstract

Wall teichoic acids (WTAs) are anionic polymers that decorate the cell walls of many Gram-positive bacteria. These structures are essential for survival or virulence in many organisms, which makes the enzymes involved in their biosynthesis attractive targets for the development of new antibacterial agents. We present a strategy to obtain WTA biosynthetic intermediates that involves a combination of chemical and enzymatic transformations. Using these intermediates, we have reconstituted the first two committed steps in the biosynthetic pathway. This work enables the exploration of WTA-synthesizing enzymes as antibiotic targets.

Published
2006
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50. ETD-Based Proteomic Profiling Improves Arginine Methylation Identification and Reveals Novel PRMT5 Substrates.

Author

Lu L, Ye Z, Zhang R, Olsen JV, Yuan Y, and Mao Y

Subjects
Humans, HeLa Cells, Protein Processing, Post-Translational, Methylation, Protein-Arginine N-Methyltransferases genetics, Protein-Arginine N-Methyltransferases metabolism, Proteomics, Arginine metabolism
Abstract

Protein arginine methylations are important post-translational modifications (PTMs) in eukaryotes, regulating many biological processes. However, traditional collision-based mass spectrometry methods inevitably cause neutral losses of methylarginines, preventing the deep mining of biologically important sites. Herein we developed an optimized mass spectrometry workflow based on electron-transfer dissociation (ETD) with supplemental activation for proteomic profiling of arginine methylation in human cells. Using symmetric dimethylarginine (sDMA) as an example, we show that the ETD-based optimized workflow significantly improved the identification and site localization of sDMA. Quantitative proteomics identified 138 novel sDMA sites as potential PRMT5 substrates in HeLa cells. Further biochemical studies on SERBP1, a newly identified PRMT5 substrate, confirmed the coexistence of sDMA and asymmetric dimethylarginine in the central RGG/RG motif, and loss of either methylation caused increased the recruitment of SERBP1 to stress granules under oxidative stress. Overall, our optimized workflow not only enabled the identification and localization of extensive, nonoverlapping sDMA sites in human cells but also revealed novel PRMT5 substrates whose sDMA may play potentially important biological functions.

Published
2024
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