4ZXP: Crystal structure of Peptidyl- tRNA Hydrolase from Vibrio cholerae

Bacterial peptidyl-tRNA hydrolase (Pth; EC hydrolyzes the peptidyl-tRNAs accumulated in the cytoplasm and thereby prevents cell death by alleviating tRNA starvation. X-ray and NMR studies of Vibrio cholerae Pth (VcPth) and mutants of its key residues involved in catalysis show that the activity and selectivity of the protein depends on the stereochemistry and dynamics of residues H24, D97, N118, and N14. D97-H24 interaction is critical for activity because it increases the nucleophilicity of H24. The N118 and N14 have orthogonally competing interactions with H24, both of which reduce the nucleophilicity of H24 and are likely to be offset by positioning of a peptidyl-tRNA substrate. The region proximal to H24 and the lid region exhibit slow motions that may assist in accommodating the substrate. Helix alpha3 exhibits a slow wobble with intermediate time scale motions of its N-cap residue N118, which may work as a flypaper to position the scissile ester bond of the substrate. Overall, the dynamics of interactions between the side chains of N14, H24, D97, and N118, control the catalysis of substrate by this enzyme.
PDB ID: 4ZXPDownload
MMDB ID: 140185
PDB Deposition Date: 2015/5/20
Updated in MMDB: 2018/07
Experimental Method:
x-ray diffraction
Resolution: 1.63  Å
Source Organism:
Similar Structures:
Biological Unit for 4ZXP: monomeric; determined by author
Molecular Components in 4ZXP
Label Count Molecule
Protein (1 molecule)
Peptidyl-trna Hydrolase(Gene symbol: VC2184)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB