Home CAS Center for Excellence


Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
Principal Investigators
WANG Enduo
Member of CAS
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Email: edwang@@sibcb.ac.cn

Research Areas
aminoacyl tRNA synthetase; aminoacylation; editing; LeuRS; ArgRS

Research Interests
The fidelity of protein synthesis is dependent on accurate substrate recognition by the aminoacyl-tRNA synthetase (aaRS) which catalyzes the first step reaction of protein biosynthesis, aminoacylation of tRNA. Each recognizes a single cognate amino acid and covalently attaches it to the correct tRNA. Some aaRSs misactivate incorrect amino acids, but have evolved mechanisms to proofread their errors and edit their mistakes. I am interested in understanding the mechanistic details and molecular interactions that govern aaRS aminoacylation and editing activities. Results from these investigations address basic research questions and also target long-term applications such as antibiotic development. My lab has focused on leucyl-, arginyl- and methionyl- tRNA synthetases to carry out the investigation.

Selected Publications

  1. 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. J. Biol. Chem.,First Published onApril 28, 2017.
  2. Ru-Juan Liu, Tao Long, Jing Li, Hao Li, En-Duo Wang*,Structural basis for substrate binding and catalytic mechanism of a human RNA:m5C methyltransferase NSun6. Nucleic Acids Res.,2017.
  3. Quan-Quan Ji, Zhi-Peng Fang, Qing Ye, Cheng-WuChi, En-Duo Wang*,Self-protective responses to norvaline-induced stress in a leucyl-tRNA synthetase editing-deficient yeast strain.Nucleic Acids Res.,2017.
  4. 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.
  5. 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 C21221.
  6. Yong Wang,Xiao-Long Zhou, Zhi-Rong Ruan, Ru-Juan Liu, Gilbert ErianiEn-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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. Hui-Yan Lei, Xiao-Long Zhou, Zhi-Rong Ruan, Wei-Cheng Sun, Gilbert ErianiEn-DuoWang*,Calpain cleaves most components in the multiple aminoacyl-tRNA synthetase complex and affects their functions.J. Biol. Chem., 2015, 290(43),26314-26327.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. 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, 477C484.
  31. 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.
  32. 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.
  33. 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), 235C247.
  34. 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.
  35. 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.
  36. 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.
  37. 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, 2010285(50), 39437-39446.
  38. 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.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. 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.
  47. 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.
  48. 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.
  49. 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.
  50. 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.

Research Team


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