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Backbone resonance assignment for the N-terminal region of bacterial tRNA-(N1G37) methyltransferase

  • Yan Li
  • Wenhe Zhong
  • Ann Zhufang Koay
  • Hui Qi Ng
  • Xiaoying Koh-Stenta
  • Qianhui Nah
  • Siau Hoi Lim
  • Andreas Larsson
  • Julien Lescar
  • Jeffrey Hill
  • Peter C. Dedon
  • CongBao Kang
Article

Abstract

Bacterial tRNA (guanine37-N1)-methyltransferase (TrmD) is an important antibacterial target due to its essential role in translation. TrmD has two domains connected with a flexible linker. The N-terminal domain (NTD) of TrmD contains the S-adenosyl-l-methionine (SAM) cofactor binding site and the C-terminal domain is critical for tRNA binding. Here we report the backbone NMR resonance assignments for NTD of Pseudomonas aeruginosa TrmD. Its secondary structure was determined based on the assigned resonances. Relaxation analysis revealed that NTD existed as dimers in solution. NTD also exhibited thermal stability in solution. Its interactions with SAM and other compounds suggest it can be used for evaluating SAM competitive inhibitors by NMR.

Keywords

TrmD tRNA methyltransferase Drug discovery Antibacterial Protein dynamics Backbone assignment 

Notes

Acknowledgements

CK appreciates the support from A*STAR JCO grant (1431AFG102/1331A028). This work is also supported by National Research Foundation of Singapore through the Singapore-MIT-Alliance for Research and Technology (SMART) Infectious Disease and Antimicrobial Resistance Interdisciplinary Research Groups. W.Z. was supported by a SMART Scholar Fellowship. We also thank Prof Ho Sup Yoon and Dr. Hong Ye from Nanyang Technological University for the supporting NMR experiments. The authors appreciate the valuable discussion from the team members at ETC, A*STAR.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Experimental Therapeutics CentreSingaporeSingapore
  2. 2.Infectious Disease and Antimicrobial Resistance Interdisciplinary Research GroupsSingapore-MIT Alliance for Research and TechnologySingaporeSingapore
  3. 3.Antimicrobial Resistance Interdisciplinary Research GroupSingapore-MIT Alliance for Research and TechnologySingaporeSingapore
  4. 4.NTU Institute of Structural BiologyNanyang Technological UniversitySingaporeSingapore
  5. 5.School of Biological SciencesNanyang Technological UniversitySingaporeSingapore
  6. 6.Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  7. 7.Department of Pathogen Biology, School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  8. 8.Experimental Biotherapeutics CentreSingaporeSingapore

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