Thienopyrimidinone derivatives that inhibit bacterial tRNA (guanine37-N1)-methyltransferase (TrmD) by restructuring the active site with a tyrosine-flipping mechanism

• Main Authors: Zhong, Wenhe, Pasunooti, Kalyan Kumar, Balamkundu, Seetharamsing, Wong, Yee Hwa, Nah, Qianhui, Gadi, Vinod, Gnanakalai, Shanmugavel, Chionh, Yok Hian, McBee, Megan E., Gopal, Pooja, Lim, Siau Hoi, Olivier, Nelson, Buurman, Ed T., Dick, Thomas, Liu, Chuan Fa, Lescar, Julien, Dedon, Peter C.
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2021
• Subjects: Science::Biological sciences; Inhibitors; Peptides and Proteins
• Online Access: https://hdl.handle.net/10356/148942
• Institution: Nanyang Technological University

Among the >120 modified ribonucleosides in the prokaryotic epitranscriptome, many tRNA modifications are critical to bacterial survival, which makes their synthetic enzymes ideal targets for antibiotic development. Here we performed a structure-based design of inhibitors of tRNA-(N1G37) methyltra...