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人才队伍

情况简介
院士风采
杰出青年
全所PI名录
 
 
地址:上海市岳阳路320号
邮编:200031
电话:86-21-54920000
传真:86-21-54921011
邮箱:sibcb@sibcb.ac.cn

全所PI名录 >

 
王恩多
研究员,中科院院士,博士生导师
E-mail: edwang@@sibcb.ac.cn


个人简介

1965-1969和1978-1981两次中国科学院上海生物化学研究所研究生毕业。1986年任生化所副研究员,1993年任研究员,博士生导师。长期以氨基酰-tRNA合成酶及其相关tRNA为对象研究酶与核酸的相互作用,以期加深人们对蛋白质生物合成质量控制机理的理解。曾获得国家自然科学二等奖,上海市自然科学一等奖、二等奖,何梁何利科技进步奖,七次中国科学院研究生导师奖,为全国劳动模范。研究所学术委员会副主任和学位评定委员会委员,中国生物化学与分子生物学常务理事,美国生物化学与分子生物学学会会员。中国科学院上海交叉学科研究中心副理事长,《生命科学》主编,《生物化学与生物物理学报》、《中国生物化学与分子生物学杂志》、《中国科学-生命科学》编委会委员。EMBO JNucleic Acids ResearchJ. Biol. Chem.Scientific Reports等杂志的审稿人。2005年当选中国科学院院士,2006年当选第三世界科学院院士。


研究方向

蛋白质生物合成的质量控制


研究工作

从事生物化学与分子生物学研究,研究方向为核酸与酶的相互作用。目前主要以tRNA和相关氨基酰-tRNA合成酶为对象进行研究。氨基酰-tRNA合成酶是蛋白质生物合成过程中的关键酶,它催化蛋白质生物合成过程中的第一步反应-tRNA氨基酰化反应。氨基酰-tRNA合成酶对tRNA的精确识别保证了遗传信息由核酸传递到蛋白质的精确性。所以研究tRNA与氨基酰-tRNA合成酶的相互作用具有重要的生物学意义。随着研究的深入,该项研究还可以为人类的疾病防止和治疗、改善人类生存环境提供理论依据和新的思路。

本研究组用分子生物学、生物化学、细胞生物学、化学和结构生物学方法,以亮氨酸tRNA/亮氨酰-tRNA合成酶(LeuRS)和精氨酸tRNA/精氨酰-tRNA合成酶(ArgRS)的系统进行“核酸与酶的相互作用”研究。目前重点研究从原核细菌到人细胞LeuRS的合成与编校功能,与编校功能有关的结构域和亮氨酸tRNA分子上的硷基,不同种属的亮氨酸tRNA/LeuRS和精氨酸tRNA/ArgRS的交叉识别,人线粒体和细胞质LeuRS和ArgRS及其与亮氨酸tRNA和精氨酸tRNA的相互作用。

研究组已发表研究论文100余篇,发表SCI收录的研究论文约80篇,其中在国外学术刊物发表55篇。研究结果400余次被包括《生物化学年鉴》和《细胞》中的综述,《美国科学院院报》,《欧洲分子生物学组织杂志》和《分子细胞》等学术刊物的研究论文引用。研究组与法国,加拿大,美国和香港等多家实验室有合作研究关系。


代表性论文

  1. Jia-Yi Fan, Qian Huang, Quan-Quan Ji, En-Duo Wang*. LeuRS can leucylate type I and type II tRNALeus in Streptomyces coelicolor. Nucleic Acids Research, 2019, Accepted.
  2. Jing Li, Hao Li, Tao Long, Han Dong, En-Duo Wang*, Liu RJ*. Archaeal NSUN6 catalyzes m5C72 modification on a wide-range of specific tRNAs, Nucleic Acids Research, 2019, 47(4), 2041-2055.
  3. Qi-Yu Zeng, Gui-Xin Peng, Guang Li, Jin-Bo Zhou, Wen-Qiang Zheng, Mei-Qin Xue, En-Duo Wang*, Zhou XL*. The G3-U70-independent tRNA recognition by human mitochondrial alanyl-tRNA synthetase, Nucleic Acids Research, 2019, 47(6), 3072-3085
  4. Preyesh Stephen, Sheng Ye, Ming Zhou, Jian Song, Rong-Guang Zhang*, En-Duo Wang*, Richard Giegé and Sheng-Xiang Lin*. Structure of Escherichia coli arginyl-tRNA synthetase in complex with tRNAArg: pivotal role of the D-loop, J. Mol. Biol. 2018, 430, 1590-1605.
  5. Yun Chen, Zhi-Rong Ruan, Yong Wang, Qian Huang, Mei-Qin Xue, Xiao-Long Zhou and En-Duo Wang* . A threonyl-tRNA synthetase-like protein has activities of tRNA aminoacylation and editing, Nucleic Acids Research, 2018, 46 (7), 3643-3656.
  6. Yong Wang, Qi-Yu, Zeng, Wen-Qiang, Zheng, Quan-Quan Ji,Xiao-Long Zhou and En-Duo Wang*. A natural non-Watson-Crick base pair in human mitochondrial tRNAThr causes structural and functional susceptibility to local mutations, Nucleic Acids Research, 2018, 46(9), 4662-4676.
  7. Taru Hilander, Xiao-Long Zhou, Svetlana Konovalova, Fu-Ping Zhang, Liliya Euro, Dmitri Chilov, Matti Poutanen, Joseph Chihade, En-Duo Wang* and Henna Tyynismaa*. Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria, Nucleic Acids Research, 2018, 46(2), 849-860.
  8. Ru-Juan Liu, Tao Long, Jin Li, Hao Li, En-Duo Wang*. Structural basis for substrate binding and catalytic mechanism of a human RNA:m5C methyltransferase NSun6. Nucleic Acids Research, 2017, 45(11), 6684-6697.
  9. Quan-Quan Ji, Zhi-Peng Fang, Qing Ye, Cheng-Wu Chi and En-Duo Wang*. Self-protective responses to norvaline-induced stress in a leucyl-tRNA synthetase editing-deficient yeast strain. Nucleic Acids Research, 2017, 45(12), 7367-7381.
  10. Qing Ye, Quan-Quan Ji, Wei Yan, Fang Yang, En-Duo Wang*. Acetylation of lysine ε-amino groups regulates aminoacyl-tRNA synthetase activity in Escherichia coli. 2017, J. Biol. Chem., 292 (25), 10709-10722.
  11. Tao Long, Jing Li, Hao Li,MiZhou, Xiao-Long Zhou, Ru-Juan Liu, En-Duo Wang*,Sequence-specific and shape-selective RNA recognition by the human RNA m5C methyltransferase NSun6. J. Biol. Chem.,2016, 291(46), 24293-24303.
  12. Xiao-Long Zhou, YunChen, Zhi-Peng Fang, Zhi-Rong Ruan, Yong Wang, Ru-Juan Liu, Mei-QinXue, En-Duo Wang*,Translational quality control by bacterial threonyl-tRNA synthetases. J. Biol. Chem.,2016, 291 (40), 21208 –21221.
  13. Yong Wang,Xiao-Long Zhou, Zhi-Rong Ruan, Ru-Juan Liu, Gilbert Eriani,En-Duo Wang*, A human disease-causing point mutation in mitochondrial threonyl-tRNA synthetase induces both structural andfunctional defects. J. Biol. Chem., 2016, 291(12), 6507-6520.
  14. Quan-Quan Ji, Zhi-Peng Fang, Qing Ye, Zhi-Rong Ruan,Xiao-Long Zhou, En-Duo Wang*, C-terminal domain of leucyl-tRNA synthetase from pathogenic Candida albicans recognizes both tRNASer and tRNALeu. J. Biol. Chem.,2016, 291 (7) , 3613-3625.
  15. Ying Yang, Wei Liu , Zhi-Peng Fang , Juan Shi, Feng-Yu Che,Chun-Xia He, Li-Bo Yao, En-Duo Wang*, Yuan-Ming Wu* , A newly Identified missense mutation in FARS2 causes autosomal-Recessive Spastic Paraplegia.Human Mutation,2016, 37 (2),165-169.
  16. Zhi-Rong Ruan,Zhi-Peng Fang, Qing Ye, Hui-Yan Lei,Gilbert Eriani, Xiao-Long Zhou*, En-Duo Wang*,Identification of lethal mutations in yeast threonyl-tRNA synthetase which reveals critical residues in its human homolog. J. Biol. Chem., 2015, 290(3), 1664-1678.
  17. Wei Yan, Qing Ye, Min Tan, Xin Chen, Gilbert Eriani, En-Duo Wang*, Modulation of aminoacylation and editing properties of leucyl-tRNA synthetase by a conserved structural module. J. Biol. Chem.,2015, 290(19), 12256-12267.
  18. Mi Zhou, Tao Long, Zhi-Peng Fang, Xiao-Long Zhou, Ru-Juan Liu*, En-Duo Wang*,Identification of determinants for tRNA substrate recognition by Escherichia coli C/U34 2’-O-methyltransferase, RNA Biol.,2015, 12(8),900-911.
  19. Ru-Juan Liu, Tao Long, Mi Zhou, Xiao-Long Zhou, En-Duo Wang*,The mechanism of ribose methylation by a bacterial SPOUT methyltransferase at position 32 in the anticodon loop of a subset of Escherichia coli tRNAs.Nucleic Acids Res.,2015, 43(15),7489-7503.
  20. Qing Ye, Meng Wang, Zhi-Peng Fang , Zhi-Rong Ruan, Quan-Quan Ji, Xiao-Long Zhou, En-Duo Wang*,Degenerate CP1 domain From Human Mitochondrial Leucyl-tRNA Synthetase. J. Biol. Chem., 2015, 290(3), 1664-1678.
  21. Hui-Yan Lei, Xiao-Long Zhou, Zhi-Rong Ruan, Wei-Cheng Sun, Gilbert Eriani,En-DuoWang*,Calpain cleaves most components in the multiple aminoacyl-tRNA synthetase complex and affects their functions.J. Biol. Chem., 2015, 290(43),26314-26327.
  22. Qian Huang, Xiao-Long Zhou, Zi-Peng Fang, Hui-Yan Lei, Qing-Hua Hu, Peng Yao, En-Duo Wang*, A bridge between the aminoacylation and editing domains of leucyl-tRNA synthetase is crucial for its synthetic activity. RNA, 2014, 20, 1440-1450.
  23. Zi-Peng Fang, Meng Wang, Zhi-Rong Ruan, Min Tan, Ru-Juan Liu, Mi Zhou, Xiao-Long Zhou* and En-Duo Wang*, Coexistence of bacterial leucyl-tRNA synthetases with archaeal tRNA binding domains that distinguish tRNALeu in the archaeal mode. Nucleic Acids Res., 2014, 42(8), 5109-5124.
  24. Fang Yang, Quan-Quan Ji, Liang-Liang Ruan, Qing Ye , En-Duo Wang*, The mRNA of Human Cytoplasmic Arginyl-tRNA Synthetase Recruits Prokaryotic Ribosomes Independently. J. Biol. Chem.,2014, 289(30), 20953-20959.
  25. Qing-Hua Hu, Ru-Juan Liu, Zi-Peng Fang, Jiong Zhang, YY Ding, Min Tan, Meng Wang, Wei Pan, Hu-Chen Zhou* and En-Duo Wang*, ZCL039, a benzoxaborole- based Streptococcus pneumoniae leucyl-tRNA synthetase inhibitor with potent antibacterial activity. Scientific Report, 2013, 3, 2475.
  26. Xiao-Long Zhou, Zhi-Peng Fang, Zhi-Rong Ruan, Meng Wang, Ruan-Juan Liu, Min Tan, Fabrizio Anella, En-Duo Wang*, Aminoacylation and translational quality control strategy employed by leucyl-tRNA synthetase from a human pathogen with genetic code ambiguity. Nucleic Acids Res., 2013, 41(21), 9825-9538.
  27. Ru-Juan Liu, Mi Zhou, Zhi-Peng Fang, Meng Wang, Xiao-Long Zhou, En-Duo Wang*, The tRNA recognition mechanism of the minimalist SPOUT methyltransferase, TrmL. Nucleic Acids Res., 2013, 41(16), 7828-7842.
  28. Tan Min, Wang Meng, Zhou Xiao-Long, Yan Wei, Eriani Gilbert and En-Duo Wang*, The Yin and Yang of tRNA: proper binding of acceptor end determines the catalytic balance of editing and aminoacylation. Nucleic Acids Res, 2013, 41(10), 5513-5523.
  29. Wei Yan, Min Tan, Gilbert Eriani, En-Duo Wang*, Leucine-specific domain modulates the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase. Nucleic Acids Res, 2013, 41(9), 4988-4998.
  30. Xiao-Long Zhou, Zhi-Rong Ruan, Qian Huang, Min Tan, En-Duo Wang*,Translational fidelity maintenance preventing Ser mis-incorporation at Thr codon in protein from eukaryote. Nucleic Acids Res, 2013, 41(1), 302-314.
  31. Qing-Hua Hu, Qian Huang, En-Duo Wang*, Crucial role of the C-terminal domain ofMycobacteriumtuberculosis leucyl-tRNA synthetase in aminoacylation and editing. Nucleic Acids Res, 2013, 41(3), 1859-1872.
  32. Meng Wang, Xiao-Long Zhou, Ru-Juan Liu, Zhi-Peng Fang, Mi Zhou, Gilbert Eriani, En-Duo Wang*, Multilevel functional and structural defects induced by two pathogenic mitochondrial tRNA mutations. Biochem. J, 2013, 453(3), 455-465.
  33. Min Tan, Bin Zhu, Ru-Juan Liu, Xin Chen, Xiao-Long Zhou, En-Duo Wang*, Inter-domain communication modulates the tRNA-dependent pre-transfer editing of leucyl-tRNA synthetase. Biochem. J., 2013,449, 123-131.
  34. Liang-Liang Ruan, Xiao-Long Zhou, Min Tan, En-Duo Wang*, Human cytoplasmic ProX edits mischarged tRNAPro with amino acid but not tRNA specificity. Biochem. J, 2013, 450, 243-252.
  35. Shuang Zhao, Lan-Tao Gou, Man Zhang, Li-Dong Zu, Min-Min Hua, Hua, Ye Hua,Hui-Juan Shi, Yong Li, Jin-Song Li, Dang-Sheng Li, En-Duo Wang*, Mo-Fang Liu*. piRNA-Triggered MIWI Ubiquitination and Removal by APC/C in Late Spermatogenesis. Developmental Cell, 2013, 24, 13-25.
  36. Qian Huang, Pen Yao, Gilbert Eriani, En-Duo Wang*, In vivo identification of essential nucleotides in tRNALeu to its functions by using a constructed yeast tRNALeu knockout strain. Nucleic Acids Res., 2012,40 (20),10463-10477.
  37. Min Tan, Wei Yan, Ru-Juan Liu, Meng Wang, Xin Chen, Xiao-Long Zhou, En-Duo Wang*, A naturally occurring nonapeptide functionally compensates for the CP1 domain of leucyl-tRNA synthetase to modulate aminoacylation activity. Biochem. J 2012,443, 477–484.
  38. Ru-Juan Liu, Min Tan, Dao-Hai Du, Bei-Si Xu, Gilbert Eriani, En-Duo Wang*, Peripheral insertion modulates editing activity of the isolated CP1 domain ofleucyl-tRNA synthetase.Biochem. J 2011, 440, 217-227.
  39. Xiao-Long Zhou, Dao-Hai Du, Min Tan, Liang-Liang Ruan, Gilbert Eriani, En-Duo Wang*, Role of tRNA amino acid-accepting end in aminoacylation and its quality control. Nucleic Acids Res, 2011, 39, 8857-8868.
  40. Xin Chen, Jing-Jing Ma, Min Tan, Peng Yao, Qing-Hua Hu, Gilbert Eriani, En-Duo Wang*, Modular pathways for editing non-cognate amino acids by human cytoplasmic leucyl-tRNA synthetase. Nucleic Acids Res., 2011, 39(1), 235–247.
  41. Min Tan, Bin Zhu, Xiao-Long Zhou, Ran He, Xin Chen, Gilbert Eriani, En-Duo Wang*, tRNA-dependent pre-transfer editing by prokaryotic leucyl-tRNA synthetase. J. Biol. Chem, 2010, 285(5), 3235-3244.
  42. Xiao-Long Zhou, Meng Wang, Min Tan, Qian Huang, Gilbert Eriani, En-Duo Wang*, Functional characterization of leucine-specific domain 1 from eukaryal and archaeal leucyl-tRNA synthetases.Biochem. J., 2010, 429, 505-513.
  43. Xiao-Long Zhou, Min Tan, Meng Wang, Xin Chen, En-Duo Wang*, Post-transfer editing by a eukaryotic leucyl-tRNA synthetase resistant to the broad-spectrum drug AN2690. Biochemical J. 2010, 430(2), 325-333.
  44. Fang Yang, Xian Xia, Hui-Yan Lei, En-Duo Wang*, Hemin binds to human cytoplasmic arginyl-tRNA synthetase and inhibits its catalytic activity. J. Biol. Chem, 2010,285(50), 39437-39446.
  45. Bin Zhu, Peng Yao, Min Tan, Gilbert Eriani, En-Duo Wang*, tRNA-independent pre-transfer editing by class I leucyl-tRNAsynthetase. J. Biol. Chem, 2009, 284, 3418-3424.
  46. Peng Yao, Bin Zhu, Yong-Gang Zheng, Gilbert Eriani, En-Duo Wang*, Recognition of tRNALeu by Aquifex aeolicus leucyl-tRNA synthetase. Nucleic Acids Res.,2008, 36(8), 2728-2738.
  47. Peng Yao, Xiao-Long Zhou, Ran He, Mei-Qin Xue, Yong-Gang Zheng, Yue-Fei Wang, En-Duo Wang*, Unique residues crucial for optimal editing in yeast cytoplasmic leucyl-tRNA synthetase are revealed by using a novel knockout yeast strain. J. Biol. Chem., 2008, 283, 22591-22600.
  48. Xiao-Long Zhou, Bin Zhu, En-Duo Wang*, The CP2 domain of leucyl-tRNA synthetase is crucial for amino acid activation and post-transfer editing, J. Biol. Chem., 2008, 283(52), 36608-36616.
  49. Bin Zhu, Ming-Wei Zhao, Gilbert Eriani,En-Duo Wang*, A present-day aminoacyl-tRNA synthetase with ancestral editing properties. RNA, 2007, 13, 15-21.
  50. Ming-Wei Zhao, Bin Zhu, Rui Hao, Min-Gang Xu, Gilbert Eriani, En-Duo Wang*, Leucyl-tRNA synthetase editing site of the ancestral bacteria Aquifex aeolicus contains relics of synthetase evolution. EMBO J., 2005, 24.1430-1439.
  51. Rui Hao, Ming-Wei Zhao, Zhan-Xi Hao, Yong-Neng Yao, En-Duo Wang*, A T-stem slip in human mitochondrial tRNALeu(CUN) regulates its charging capacity. Nucleic Acids Res., 2005, 33(11), 3606-3613.
  52. Chen Ling, Yong-Neng Yao, Yong-Gang Zheng, Hui Wei, Lie Wang, Xiang-Fu Wu, En-Duo Wang*, The C-terminal appended domain of human cytosolic leucyl-tRNA synthetase is indispensable in its interaction with arginyl-tRNA synthetase in the multi-tRNA synthetase complex. J. Biol. Chem., 2005, 280(41), 34755-34763.
  53. Yong-Gang Zheng, Hui Wei, Chen Ling, Franck Martin, Gilbert Eriani, En-Duo Wang*, Two distinct domains of the b subunit of Aquifex aeolicus leucyl-tRNA synthetase are involved in tRNA binding as revealed by a three-hybrid selection. Nucleic Acids Res., 2004, 32, 3294-3303.
  54. Min-Gang Xu, Ming-Wei Zhao, En-Duo Wang*, Leucyl-tRNAsynthetase from the hyperthermophilic bacterium Aquifexaeolicus recognizes minihelices. J. Biol. Chem., 2004, 279, 32151-32158.
  55. Xing Du, En-Duo Wang*, Tertiary-structure base pairs between D-and TYC- loops of Escherichia coli tRNALeu play important roles in both aminoacylation and editing. Nucleic Acids Res., 2003, 31 (11), 2865-2872.
  56. Juan Li, Yong-neng Yao, Mo-Fang Liu, En-Duo Wang*, Arginyl-tRNAsynthetase with signature sequence KMSK from Bacillus stearothermophilus. Biochem. J., 2003, 376 (3), 773-779.
  57. Min-Gang Xu, Jian-Feng Chen, Franck Martin, Gilbert Eriani, En-Duo Wang*, Leucyl-tRNAsynthetase consisting of two subunits from hyper thermophilic bacterium Aquifex aeolicus. J. Biol. Chem., 2002, 277(44), 41590-41596.

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