Jingjing Zhuang

Structure-Based Optimization of HIF-2α Agonists That Synergistically Enhance Erythropoietin Production with PHD Inhibitors

Weiwei Xu, Zhifang Bai, Keming Chen, Fengyao Li et autres

Abstract Hypoxia-inducible factor 2α (HIF-2α) is a crucial transcription factor regulating various physiological processes, including angiogenesis and erythropoiesis. The activity of HIF-2α is mainly controlled through oxygen-dependent protein hydroxylation, mediated by prolyl hydroxylase domain (PHD) enzymes, leading to subsequent HIF-2α ubiquitination and …

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Molecular mechanism of the crosstalk between glucocorticoid receptor (GR) and hypoxia-inducible factor 3α (HIF-3α) pathways

Meina Zhang, Xiaotong Diao, Mengqi Guo, Xiangnan Sun et autres

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Hosts and Commensal Bacteria Synergistically Antagonize Opportunistic Pathogens at the Single‐Cell Resolution

Sheng Zhang, Ziguang Wang, Anqi Liu, Jinshu Li et autres

Natural microbes coexist in a diverse species population with competition for space and nutrient resources. However, the molecular mechanisms underpinning the regulatory networks of microbes among themselves and with their host are still in infancy. Here, it is reported that Drosophila and …

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Structural basis for the ligand-dependent activation of heterodimeric AHR-ARNT complex

Xiaotong Diao, Qinghong Shang, Mengqi Guo, Yubin Huang et autres

The aryl hydrocarbon receptor (AHR) possesses an extraordinary capacity to sense and respond to a wide range of small-molecule ligands, ranging from polycyclic aromatic hydrocarbons to endogenous compounds. Upon ligand binding, AHR translocates from the cytoplasm to nucleus, forming a transcriptionally active …

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Two natural compounds as potential inhibitors against the Helicobacter pylori and Acinetobacter baumannii IspD enzymes

Xiaoyu Chen, Huilin Zhao, Chuandong Wang, Mostafa M. Hamed et autres

In a vast majority of bacteria, protozoa and plants, the methylerythritol phosphate (MEP) pathway is utilized for the synthesis of isopentenyl diphosphate (IDP) and dimethylallyl diphosphate (DMADP), which are precursors for isoprenoids. Isoprenoids, such as cholesterol and coenzyme Q, play a variety …

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Sporisorium reilianum polysaccharides improve DSS-induced ulcerative colitis by regulating intestinal barrier function and metabolites

Shuaichen Liu, Lan Hong, Song Zhang, Yuxin Tian et autres

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Cyclic peptides discriminate BCL-2 and its clinical mutants from BCL-XL by engaging a single-residue discrepancy

Fengwei Li, Jun-Jie Liu, Chao Liu, Ziyan Liu et autres

Abstract Overexpressed pro-survival B-cell lymphoma-2 (BCL-2) family proteins BCL-2 and BCL-XL can render tumor cells malignant. Leukemia drug venetoclax is currently the only approved selective BCL-2 inhibitor. However, its application has led to an emergence of resistant mutations, calling for drugs with …

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Decoding Allosteric Control in Hypoxia-Inducible Factors

Jingjing Zhuang, Qinghong Shang, Fraydoon Rastinejad, Dalei Wu

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Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family

Xiangnan Sun, Linqian Jing, Fengwei Li, Meina Zhang et autres

Neuronal PER-ARNT-SIM (PAS) domain protein 4 (NPAS4) is a protective transcriptional regulator whose dysfunction has been linked to a variety of neuropsychiatric and metabolic diseases. As a member of the basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) transcription factor family, NPAS4 is distinguished by an …

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SAR study of 1,2-benzisothiazole dioxide compounds that agonize HIF-2 stabilization and EPO production

Wanbin Song, Jingjing Zhuang, Nan Zhang, Xintong Ren et autres

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Structural Basis for the Allosteric Inhibition of Hypoxia-Inducible Factor 2 by Belzutifan

Xintong Ren, Xiaotong Diao, Jingjing Zhuang, Dalei Wu

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Identification of oleoylethanolamide as an endogenous ligand for HIF-3α

Xiaotong Diao, Fei Ye, Meina Zhang, Xintong Ren et autres

Hypoxia-inducible factors (HIFs) are α/β heterodimeric transcription factors modulating cellular responses to the low oxygen condition. Among three HIF-α isoforms, HIF-3α is the least studied to date. Here we show that oleoylethanolamide (OEA), a physiological lipid known to regulate food intake and …

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