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991.
Li-Quan Yang Yi-Rui Yin Jian-Xin Shen Yi Li 《Journal of biomolecular structure & dynamics》2020,38(9):2768-2776
Communicated by Ramaswamy H. Sarma 相似文献
992.
Zhiwei Yang Yizhen Zhao Dongxiao Hao Shunlin Ren Xiaohui Yuan Lingjie Meng 《Journal of biomolecular structure & dynamics》2020,38(7):1918-1926
AbstractPeroxisome proliferator-activated receptor gamma (PPARγ) has recently been identified as an attractive target for atherosclerosis intervention. Given potential relevance of 5-cholesten-3β, 25-diol, 3-sulphate (CHOS) and PPARγ, an integrated docking method was used to study their interaction mechanisms, with the full considerations to distinct CHOS conformations and dynamic ensembles of PPARγ ligand-binding domain (PPARγ-LBD). The results revealed that this novel platform is satisfactory to the accurate determination of binding profiles, and the binding pattern of CHOS is rather similar as those of current PPARγ full/partial agonists. CHOS contributes to the stabilization of the AF2 and β-sheet surfaces of PPARγ-LBD and promotes the configuration adjustment of Ω loop, in order to inhibit the Cdk5-mediated PPARγ phosphorylation. Nonetheless, there are clear differences in term of occupation of full or partial agonist-like binding models. The energetic and geometric analyses further revealed that CHOS may be fond of partial agonist-like binding, and its sulfonic group and carbon skeleton are helpful for the binding process. We hope that the results will aid our understanding of recognitions involving CHOS with PPARγ-LBD and warrant the further aspects to pharmacological experiments.Communicated by Ramaswamy H. Sarma 相似文献
993.
Shang-Ling Xiong Gyu Tae Lim Shang-Jun Yin Jinhyuk Lee Jae-Rin Lee Myong-Joon Hahn 《Journal of biomolecular structure & dynamics》2020,38(12):3496-3503
AbstractThe inhibition of α-glucosidase is used as a key clinical approach to treat type 2 diabetes mellitus and thus, we assessed the inhibitory effect of α-ketoglutaric acid (AKG) on α-glucosidase with both an enzyme kinetic assay and computational simulations. AKG bound to the active site and interacted with several key residues, including ASP68, PHE157, PHE177, PHE311, ARG312, TYR313, ASN412, ILE434 and ARG439, as detected by protein–ligand docking and molecular dynamics simulations. Subsequently, we confirmed the action of AKG on α-glucosidase as mixed-type inhibition with reversible and rapid binding. The relevant kinetic parameter IC50 was measured (IC50 = 1.738?±?0.041?mM), and the dissociation constant was determined (Ki Slope = 0.46?±?0.04?mM). Regarding the relationship between structure and activity, a high AKG concentration induced the slight modulation of the shape of the active site, as monitored by hydrophobic exposure. This tertiary conformational change was linked to AKG inhibition and mostly involved regional changes in the active site. Our study provides insight into the functional role of AKG due to its structural property of a hydroxyphenyl ring that interacts with the active site. We suggest that similar hydroxyphenyl ring-containing compounds targeting key residues in the active site might be potential α-glucosidase inhibitors. Abbreviations AKG alpha-ketoglutaric acid pNPG 4-nitrophenyl-α-d-glucopyranoside ANS 1-anilinonaphthalene-8-sulfonate MD molecular dynamics. Communicated by Ramaswamy H. Sarma 相似文献
994.
Zhang Jinxiu Feng Haiyan Lv Jianhua Zhao Liqiang Zhao Junxia Wang Li-an 《Molecular and cellular biochemistry》2020,474(1-2):277-284
Molecular and Cellular Biochemistry - Autism is a prevalent developmental disorder that combines repetitive behaviours, social deficits and language abnormalities. The present study aims to assess... 相似文献
995.
Yin Wenchao Wang Chunyan Peng Yue Yuan Wenlin Zhang Zhongjun Liu Hong Xia Zhengyuan Ren Congcai Qian Jinqiao 《Molecular biology reports》2020,47(5):3629-3639
Molecular Biology Reports - Oxidative stress induced necroptosis is important in myocardial ischemia/reperfusion injury. Dexmedetomidine (Dex), an α2-adrenoceptor (α2-AR) agonist, has... 相似文献
996.
Radiation and Environmental Biophysics - Objective of the present study was to investigate the tolerant radiation dose of nasal mucosa by observing and analyzing patients who received... 相似文献
997.
Mengmeng Han Jialun Li Yaqiang Cao Yuanyong Huang Wen Li Haijun Zhu Qian Zhao Jing-Dong Jackie Han Qihan Wu Jiwen Li Jing Feng Jiemin Wong 《Nucleic acids research》2020,48(21):12116
LSH, a SNF2 family DNA helicase, is a key regulator of DNA methylation in mammals. How LSH facilitates DNA methylation is not well defined. While previous studies with mouse embryonic stem cells (mESc) and fibroblasts (MEFs) derived from Lsh knockout mice have revealed a role of Lsh in de novo DNA methylation by Dnmt3a/3b, here we report that LSH contributes to DNA methylation in various cell lines primarily by promoting DNA methylation by DNMT1. We show that loss of LSH has a much bigger effect in DNA methylation than loss of DNMT3A and DNMT3B. Mechanistically, we demonstrate that LSH interacts with UHRF1 but not DNMT1 and facilitates UHRF1 chromatin association and UHRF1-catalyzed histone H3 ubiquitination in an ATPase activity-dependent manner, which in turn promotes DNMT1 recruitment to replication fork and DNA methylation. Notably, UHRF1 also enhances LSH association with the replication fork. Thus, our study identifies LSH as an essential factor for DNA methylation by DNMT1 and provides novel insight into how a feed-forward loop between LSH and UHRF1 facilitates DNMT1-mediated maintenance of DNA methylation in chromatin. 相似文献
998.
Li Yan-mei Wang Meng Wang Tian-yun Wei Yong-ge Guo Xiao Mi Chun-liu Zhao Chun-peng Cao Xiang-xiang Dou Yuan-yuan 《Molecular biology reports》2020,47(1):469-475
Molecular Biology Reports - Multicistronic vectors can increase transgene expression and decrease the imbalance of gene expression in the Chinese hamster ovary (CHO) cell expression system. Small,... 相似文献
999.
Duan Xianlan Zhao Lian Jin Wancun Xiao Qinxin Peng Yani Huang Gan Li Xia DaSilva-Arnold Sonia Yu Haibo Zhou Zhiguang 《Molecular biology reports》2020,47(10):7557-7566
Molecular Biology Reports - The main pathogenesis of type 1 diabetes mellitus (T1DM) is autoimmune-mediated apoptosis of pancreatic islet β cells. We sought to characterize the function of... 相似文献
1000.
Molecular Biology Reports - Chondrocytes are the sole cell type present within cartilage, and play pivotal roles in controlling the formation and composition of health cartilage. Chondrocytes... 相似文献