Structures of new crystal forms of Mycobacterium tuberculosis peptidyl-tRNA hydrolase and functionally important plasticity of the molecule

Abstract

The X-ray structures of new crystal forms of peptidyl-tRNA hydrolase from M. tuberculosis reported here and the results of previous X-ray studies of the enzyme from different sources provide a picture of the functionally relevant plasticity of the protein molecule. The new X-ray results confirm the connection deduced previously between the closure of the lid at the peptide-binding site and the opening of the gate that separates the peptide-binding and tRNA-binding sites. The plasticity of the molecule indicated by X-ray structures is in general agreement with that deduced from the available solution NMR results. The correlation between the lid and the gate movements is not, however, observed in the NMR structure.

Figure 1

Overall structure of MtPth viewed from nearly opposite directions. The rigid (blue) and flexible regions (red) of the molecule (see text) are indicated. The locations of the ‘lid’ and ‘gate’ are also indicated.

Figure 2

The C-terminal stretch as observed in MtPth form II molecule B (blue), MtPth form IV (green), MtPth form V (red), EcPth (brown), MsPth (magenta) and FtPth (grey).

Figure 3

Conformation of the lid in MtPth form I (blue), MsPth (magenta), EcPth (brown) and FtPth (cyan).

Figure 4

Correlation between gate and lid distances in (a) available crystal structures and (b) NMR structures.