Enzymatic Dynamics and Inhibition of Bacterial Pth1
P. aeruginosa peptidyl-tRNA hydrolase (Pth1) - PDB ID 4FYJ
Bacterial peptidyl-tRNA hydrolase (Pth1)
Multi-drug resistant bacteria have become an emerging problem with the normalization of modern antibiotics. Now it has become even more important to discover new targets for antibiotic development. Bacterial peptidyl-tRNA hydrolase (Pth1) is one such solution that has shown evidence of being a viable novel antibiotic target.
Bacterial peptidyl-tRNA hydrolase 1 (Pth1) is essential to bacterial cells. It functions to release peptides from peptidyl-tRNA that result from ribosome stalling or expression of ORFs. Pth1 does this by cleaving the ester bond between the peptide and the tRNA. Without this enzyme, the cell cannot recycle its tRNA for translation and will die from tRNA starvation. This makes inhibition of this enzyme a novel strategy for antibiotic development as there are less Pth1 enzymes than ribosomes. Additionally, bacteria possess only a single type of Pth1 that is structurally and mechanistically different from the several orthologous Pth enzymes in eukaryote. This means bacterial Pth1 could be inhibited while having a minimal effect on humans.
Meredyth is a new student to the group. Her project in the Baudry lab is a collaboration with UAH professor Dr. McFeeters and his current Pth1 research. Meredyth seeks to use various computational methods to unearth the molecular and physical dynamics of the Pseudomonas aeruginosa Pth1 enzyme and to be able to screen for small molecule inhibition. Upon successful collection of potential drug-able inhibitors, Meredyth will further test the compounds in wet lab.