Computational modeling and molecular dynamics simulations of mammalian cytoplasmic tyrosyl-tRNA synthetase and its complexes with substrates.

Cytoplasmic tyrosyl-tRNA synthetase (TyrRS) is one of the key enzymes of protein biosynthesis. TyrRSs of pathogenic organisms have gained attention as potential targets for drug development. Identifying structural differences between various TyrRSs will facilitate the development of specific inhibitors for the TyrRSs of pathogenic organisms.

Interdomain compactization in human tyrosyl-tRNA synthetase studied by the hierarchical rotations technique.

Aminoacyl-tRNA synthetases are key enzymes of protein biosynthesis which usually possess multidomain structures. Mammalian tyrosyl-tRNA synthetase is composed of two structural modules: N-terminal catalytic core and an EMAPII-like C-terminal domain separated by long flexible linker. The structure of full-length human cytoplasmic tyrosyl-tRNA synthetase is still unknown.

[A model of three-dimensional structure of Mycobacterium tuberculosis tyrosyl-tRNA synthetase].

The search of new effective antibacterial drugs against infectious agents also lately include inhibitors of some aminoacyl-tRNA synthetases. In this regard, tyrosyl-tRNA synthetase from M. tuberculosis (MtTyrRS) is one of especially attractive target due to its key role in cell metabolism and significant differences between spatial structures of eubacterial and human TyrRSs.

[Computer modeling of cytochrome P450 2E1 three-dimensional structure].

A computer model of human cytochrome P450 2E1 (CYP2E1) three-dimensional structure and active site was constructed based on homology with crystallographic coordinates of CYP2C5 and CYP2C9. A high degree of secondary structure homology for human, mouse, rat and rabbit CYP2E1 was demonstrated. The location of heme and the supporting alpha-helices was established.

[Production of polyclonal antibodies to tyrosyl-tRNA-synthetase from the bovine liver and characterization of two forms of the enzyme].

The polyclonal antibodies purified by affine chromatography against tyrosyl-tRNA synthetase (TyrRS) immobilized on the column with affigel-sepharose have been obtained from the bovine liver. The immunospecificity of these antibodies and their influence on enzymatic activity of TyrRS from the bovine liver have been investigated. We have stated that the polyclonal antibodies inhibited TyrRS enzymatic activity in aminoacylation of homologous tRNA(Tyr) by 47%.