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Computational Molecular Bioscience 2015年第2期5卷 13-19页

作者： Ehsan Heidari Soureshjani Ali Kazemi Babaheydari Elahe Saberi Young Researcher and Elites Club Islamic Azad University Shahrekord Branch Shahrekord Iran Faculty of Science Department of Chemistry Islamic Azad University Shahrekord Branch Shahrekord Iran Faculty of Basic Sciences Department of Biology Shahrekord Branch Islamic Azad University Sahrekord Iran

DNA methyltransferases 1 (DNMT1) has been looked as crucial targets against various types of cancers. MD simulations have advanced to a point where the atomic level information of biological macromolecule (protein or DNA-protein or protein-protein) can easily be advantageous to predict the functionality. In this study we utilize xanthomicrol and galloyl compounds to investigate potential compounds for the inhibition of DNMT1, and the results of these two compounds are compared with drug decitabine. Xanthomicrol and galloyl are found to dock successfully within the active site of DNMT1. A comparison of the inhibitory potential of screened xanthomicrol inhibited DNMT1 approximately is identical with those of their corresponding drugs, decitabine. The stability of the DNMT1 with the best docked xanthomicrol, were further analysed in molecular dynamics (MD) simulation and compared with those of the respective drugs namely decitabine which revealed stabilization of these complexes within 300 ns of simulation with better stability of DNMT1.

关键词： DNA methyltransferases 1 Decitabine Molecular Dynamics Galloyl Xanthomicrol

Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease

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World Journal of Hepatology 2024年第5期16卷 703-715页

作者： Li Xu Yu-Hong Fan Xiao-Jing Zhang Lan Bai State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases Gannan Innovation and Translational Medicine Research InstituteGannan Medical UniversityGanzhou 341000China School of Basic Medical Sciences Wuhan UniversityWuhan 430060China

Non-alcoholic fatty liver disease(NAFLD)poses a significant health challenge in modern societies due to shifts in lifestyle and dietary *** complexity stems from genetic predisposition,environmental influences,and metabolic *** processes govern various cellular functions such as transcription,chromatin structure,and cell *** NAFLD,these epigenetic tendencies,especially the process of histone methylation,are intricately intertwined with fat accumulation in the *** methylation is regulated by different enzymes like methyltransferases and demethylases and influences the expression of genes related to *** early-stage NAFLD is reversible,its progression to severe stages becomes almost ***,early detection and intervention in NAFLD are crucial,and understanding the precise role of histone methylation in the early stages of NAFLD could be vital in halting or potentially reversing the progression of this disease.

关键词： Non-alcoholic fatty liver disease Mechanism Histone methylation methyltransferases Demethytrasferases Epigenetic modification Adipogenesis

Methylation in hangtaimycin biosynthesis and its antibacterial activities

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Synthetic and Systems Biotechnology 2023年第4期8卷 682-687页

作者： Minghe Luo Yulu Dong Zixin Deng Yuhui Sun School of Pharmacy and Bioengineering Chongqing University of TechnologyChongqingChina Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Educationand School of Pharmaceutical SciencesWuhan UniversityWuhanChina

About two-thirds of small molecule drugs contain methyl group and it plays a very important role in the drug ***,methyltransferases catalyzing the methylation have always attracted great ***(HTM)is a potent hepatoprotective *** study showed that its biosynthetic gene cluster contained three methyltransferase domains,but their characteristics in HTM biosynthetic pathway has not been *** this study,we clarified multi-methylations in HTM biosynthesis in *** showed that the two S-adenosylmethionine-dependent methyltransferases(SAM-MTs)of HtmA2(-module 6)-MT domain and HtmB2(-module 18)-MT domain are responsible for the installation of methyl group at C-45 and N-12,respectively,whereas the FK506 methyltransferase(FKMT)type O-methyltransferase of HtmB1(-module 16)-MT domain take care of the methylation at O-21 of *** also reported the antibacterial activities of HTM in this study,and found that it showed activities against ***,*** and *** with MIC of 4μg/mL,4μg/mL,and 64μg/mL,respectively.

关键词： Hangtaimycin Methylation S-Adenosylmethionine-dependent methyltransferases FK506 methyltransferase type O-methyltransferase Antibacterial Biosynthesis

Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease

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World Journal of Gastroenterology 2010年第25期16卷 3187-3195页

作者： Xian-Wen Dong Qing Zheng Ming-Ming Zhu Jing-Lu Tong Zhi-Hua Ran Department of Gastroenterology Renji Hospital Shanghai Institute of Digestive Disease Shanghai Jiao Tong University School of Medicine Shanghai 200001China

AIM: To evaluate the relationship between thiopu- rine S-methyltransferase (TPMT) polymorphisms and thiopurine-induced adverse drug reactions (ADRs) in inflammatory bowel disease (IBD). METHODS: Eligible articles that compared the frequency of TPMT polymorphisms among thiopurine-tolerant and-intolerant adult IBD patients were included. Statistical analysis was performed with Review Manager 5.0. Sub-analysis/sensitivity analysis was also performed. RESULTS: Nine studies that investigated a total of 1309 participants met our inclusion criteria. The inci- dence of TPMT gene mutation was increased 2.93-fold (95% CI: 1.68-5.09, P = 0.0001) and 5.93-fold (95% CI: 2.96-11.88, P < 0.00001), respectively, in IBD patients with thiopurine-induced overall ADRs and bone marrow toxicity (BMT), compared with controls. The OR for TPMT gene mutation in IBD patients withthiopurine-induced hepatotoxicity and pancreatitis was 1.51 (95% CI: 0.54-4.19, P = 0.43) and 1.02 (95% CI: 0.26-3.99, P = 0.98) vs controls, respectively. CONCLUSION: This meta-analysis suggests that the TPMT polymorphisms are associated with thiopurine-induced overall ADRs and BMT, but not with hepatotoxicity and pancreatitis.

关键词： methyltransferases Inflammatory bowel diseases Meta-analysis Adverse drug reactions Bone marrow toxicity

Role of transmethylation reactions in alcoholic liver disease

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World Journal of Gastroenterology 2007年第37期13卷 4947-4954页

作者： Kusum K Kharbanda VA Alcohol Research Center Department of Veterans Affairs Medical Center Omaha Nebraska 68105 United States Department of Internal Medicine University of Nebraska Medical Center Omaha Nebraska 68198 United States

Alcoholic liver disease is a major health care problem worldwide. Findings from many laboratories, including ours, have demonstrated that ethanol feeding impairs several of the many steps involved in methionine metabolism. Ethanol consumption predominantly results in a decrease in the hepatocyte level of S-adenosylmethionine and the increases in two toxic metabolites, homocysteine and S-adenosylhomocysteine. These changes, in turn, result in serious functional consequences which include decreases in essential methylation reactions v/a inhibition of various methyltransferases. Of particular interest to our laboratory is the inhibition of three important enzymes, phosphatidylethanolamine methyltransferase, isoprenylcysteine carboxyl methyltransferase and protein L-isoaspartate methyltransferase. Decreased activity of these enzymes results in increased fat deposition, increased apoptosis and increased accumulation of damaged proteins- all of which are hallmark features of alcoholic liver injury. Of all the therapeutic modalities available, betaine has been shown to be the safest, least expensive and most effective in attenuating ethanol-induced liver injury. Betaine, by virtue of aiding in the remethylation of homocysteine, removes both toxic metabolites （homocysteine and S-adenosylhomocysteine）, restores S-adenosylmethionine level, and reverses steatosis, apoptosis and damaged proteins accumulation. In conclusion, betaine appears to be a promising therapeutic agent in relieving the methylation and other defects associated with alcoholic abuse.

关键词： Transmethylation S-adenosylhomocysteine Alcohol Betaine Liver Steatosis Apoptosis methyltransferases

蛋白质精氨酸甲基转移酶1调控DNA损伤修复和细胞凋亡

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海洋科学 2020年第3期44卷 146-152页

作者：张一超吴韦韦李奥刘宝华庞秋香山东理工大学生命科学学院山东淄博255049 深圳大学基础医学院广东深圳518060

蛋白质精氨酸甲基转移酶1 (protein arginine methyltransferases 1, PRMT1)是PRMT家族中的重要一员,属于Ⅰ型PRMTs,细胞内超过85%的蛋白质精氨酸的甲基化由其催化。PRMT1通过调节底物的甲基化水平,从而调控蛋白的功能及蛋白参与的细胞... 详细信息

蛋白质精氨酸甲基转移酶1 (protein arginine methyltransferases 1, PRMT1)是PRMT家族中的重要一员,属于Ⅰ型PRMTs,细胞内超过85%的蛋白质精氨酸的甲基化由其催化。PRMT1通过调节底物的甲基化水平,从而调控蛋白的功能及蛋白参与的细胞活动和生理过程,包括细胞信号转导,DNA损伤修复,转录调控,RNA代谢,蛋白质相互作用等。本文着重讨论PRMT1的结构、底物及其在DNA损伤修复和细胞凋亡中的功能。

关键词： PRMT1(protein arginine methyltransferases 1) 甲基化 DNA损伤修复细胞凋亡

Comparison of global DNA methylation profiles in replicative versus premature senescence

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Comparison of global DNA methylation profiles in replicative...

Effect of DNA methylation on heat resistant properties of Lentinula edodes

中国毒理学会生化与分子毒理专业委员会第六届全国学术会议、中国毒理学会遗传毒理专业委员会第五届全国学术会议、广东省预防医学会卫生毒理专业委员会学术会议、广东省环境诱变剂学会学术会议

作者： Wen juan Zhang~(a,b) Weidong Ji~(a,b,c) Jianping Yang~a Linqing Yang~b Jianhui Yuan~b Yuling Xu~(a,b) Wei Xu~(a,b) Wen Chen~a Zhixiong Zhuang~(b,*) ~a School of Public Health,Sun Yet-sen University,74 Zhongshan Road 2,Guangzhou 510080,P.R.China ~b Shenzhen Center for Disease Control and Prevention,21 Tianbei Road 1,Shenzhen 518020,P.R.China:~c Institute for Chemical Carcinogenesis,Guangzhou Medical College,195 Dongfeng Xi Road,Guangzhou 510182,P.R.China

DNA methylation is considered to play an essential role in cellular senescence. To uncover the mechanism underlying cellular senescence,we established the model of premature senescence induced by hydrogen peroxide （HO） in human embryonic lung fibroblasts and investigated the changes of genome methylation,DNA methyltransferases （DNMTs） and DNA-binding domain proteins （MBDs） in comparison with those observed during normal replicative *** found that premature senescence triggered by HO exhibited distinct morphological characteristics and proliferative capacity which were similar to those of replicative *** genome methylation level decreased gradually during the premature as well as replicative senescence,which was associated with the reduction in the expression of DNMTI,reflecting global hypomethylation as a distinct feature of senescent *** levels of DNMT3b and methyl-CpG binding protein 2 （MeCP2） increased in both mid-aged and replicative senescent cells,while DNMT3a and MBD2 were upregulated in the mid-aged *** DNMT3b was elevated in the cells in the premature senescence persistence ***,the expression for DNMTs, MBD2 and MeCP2 was increased rapidly upon HO *** results indicate that HO-induced premature senescence share some features of replicative senescence,such as basic biological characteristics and global hypomethylation while there are slight differences in the profile of methylation-associated enzyme *** damage may hence be a causative factor in epigenetic alteration partly responsible for cellular senescence.

关键词： methylation senescence methyltransferases hydrogen peroxide

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Effect of DNA methylation on heat resistant properties of Le...

Regulation of DNA methylation on development and aflatoxin metabolism of Aspergillus flavus

多彩菌物美丽中国——中国菌物学会2019年学术年会

作者： SONG Shuang LIU Yu WANG Shouxian SONG Qinggang Institute of Plant and Environment Protection Beijing Academy of Agriculture and Forestry Sciences Beijing Engineering Research Center for Edible Mushroom

DNA methylation plays an important role in biological processes through stabilizing genomic structure and regulating gene expression. Heat-resistant strain and heat-sensitive strain of Lentinula edodes were used as materials to analyze the methylation level and methylation patterns of genomic DNA after high temperature *** results showed that the methylation level of both shiitake strains increased after heat treatment, but the methylation level of heat-resistant strain changed more than that of heat-sensitive strain. DNA methylation and demethylation happened in both strains at the same time, but the changing patterns were different. The expression levels of DNA methyltransferases, key enzymes in DNA methylation process, were detected. The expression of two methyltransferase genes significantly increased after high temperature stress. After inhibition of methyltransferase activity, the heat resistant properties of Lentinula edodes strain showed a downward trend.

关键词： DNA methylation Heat stress Lentinula edodes methyltransferases

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Regulation of DNA methylation on development and aflatoxin m...