Peptidyl-tRNA hydrolase cleaves the
ester bond between
tRNA and the attached
peptide in
peptidyl-tRNA in order to avoid the toxicity resulting from its accumulation and to free the
tRNA available for further rounds in
protein synthesis. The structure of the
enzyme from Mycobacterium tuberculosis has been determined in three crystal forms. This structure and the structure of the
enzyme from Escherichia coli in its crystal differ substantially on account of the binding of the C terminus of the E. coli
enzyme to the
peptide-binding site of a neighboring molecule in the crystal. A detailed examination of this difference led to an elucidation of the plasticity of the binding site of the
enzyme. The
peptide-binding site of the
enzyme is a cleft between the body of the molecule and a
polypeptide stretch involving a loop and a helix. This stretch is in the open conformation when the
enzyme is in the free state as in the crystals of M.
tuberculosis peptidyl-tRNA hydrolase. Furthermore, there is no physical continuity between the
tRNA and the
peptide-binding sites. The molecule in the E. coli crystal mimics the
peptide-bound
enzyme molecule. The
peptide stretch referred to earlier now closes on the bound
peptide. Concurrently, a channel connecting the
tRNA and the
peptide-binding site opens primarily through the concerted movement of two residues. Thus, the crystal structure of M.
tuberculosis peptidyl-tRNA hydrolase when compared with the crystal structure of the E. coli
enzyme, leads to a model of structural changes associated with
enzyme action on the basis of the plasticity of the molecule.