Mykulyak V. Molecular dynamics of Mycobacterium tuberculosis tyrosyl-tRNA synthetase and formation of metastable elements in the active sitе

The present study is dedicated to the investigation of molecular dynamics of Mycobacterium tuberculosis tyrosyl-tRNA synthetase in water-ion solution. The work studied the dynamics of enzyme in the free state and in complexes with different substrates and inhibitors. It has been shown for the first time dynamic formation of antiparallel strands in unstructured KMSKS-like catalytic loop, which is typical for class I of aminoacyl-tRNA synthetases. It was found that ?-strands dynamically forming in the course of enzyme molecular dynamics kept catalytic loop in "closed" state, directing KMSKS-like catalytic motif into the active site. Based on structure of bacterial tyrosyl-tRNA synthetase inhibitor SB-219383, design of new inhibitors of the enzyme was conducted.