西亚试剂：：Crucial role of the C-terminal domain ofMycobacterium

Qing-Hua Hu, Qian Huang and En-Duo Wang*

The C-terminal extension of prokaryotic leucyl-tRNA synthetase (LeuRS) has been shown to make contacts with the tertiary structure base pairs of tRNALeu as well as its long variable arm. However, the precise role of the flexibly linked LeuRS C-terminal domain (CTD) in aminoacylation and editing processes has not been clarified. In this study, we carried out aspartic acid scanning within the CTD of Mycobacterium tuberculosisLeuRS (MtbLeuRS) and studied the effects on tRNALeu-binding capacity and enzymatic activity. Several critical residues were identified to impact upon the interactions between LeuRS and tRNALeu due to their contributions in the maintenance of structural stability or a neutral interaction interface between the CTD platform and tRNALeu elbow region. Moreover, we propose Arg921 as a crucial recognition site for the tRNALeulong variable arm in aminoacylation and tRNA-dependent pre-transfer editing. We also show here the CTD flexibility conferred by Val910 in regulation of LeuRS–tRNALeu interaction. Taken together, our results suggest the structural importance of the CTD in modulating precise interactions between LeuRS and tRNALeu during the quality control of leucyl-tRNALeu synthesis. This system for the investigation of the interactions between MtbLeuRS and tRNALeu provides a platform for the development of novel antitubercular drugs.

丙烯醛肉桂醛桂皮醛4-硝基肉桂醛