Int. J. Mol. Sci. 2013, 14(11), 22741-22752; doi:10.3390/ijms141122741
Article

Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA

1 Department of Chemistry, University of Alabama in Huntsville, 301 Sparkman Drive, Huntsville, AL 35899, USA 2 Oak Ridge National Laboratory, Biology and Soft Matter Division, P.O. Box 2008, Oak Ridge, TN 37831, USA These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 9 October 2013; in revised form: 31 October 2013 / Accepted: 12 November 2013 / Published: 19 November 2013
PDF Full-text Download PDF Full-Text [785 KB, uploaded 19 November 2013 10:44 CET]
Abstract: Bacterial Pth1 is essential for viability. Pth1 cleaves the ester bond between the peptide and nucleotide of peptidyl-tRNA generated from aborted translation, expression of mini-genes, and short ORFs. We have determined the shape of the Pth1:peptidyl-tRNA complex using small angle neutron scattering. Binding of piperonylpiperazine, a small molecule constituent of a combinatorial synthetic library common to most compounds with inhibitory activity, was mapped to Pth1 via NMR spectroscopy. We also report computational docking results, modeling piperonylpiperazine binding based on chemical shift perturbation mapping. Overall these studies promote Pth1 as a novel antibiotic target, contribute to understanding how Pth1 interacts with its substrate, advance the current model for cleavage, and demonstrate feasibility of small molecule inhibition.
Keywords: peptidyl-tRNA hydrolase; small angle neutron scattering; enzyme-substrate complex; docking; inhibition

Article Statistics

Load and display the download statistics.

Citations to this Article

Cite This Article

MDPI and ACS Style

Hames, M.C.; McFeeters, H.; Holloway, W.B.; Stanley, C.B.; Urban, V.S.; McFeeters, R.L. Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA. Int. J. Mol. Sci. 2013, 14, 22741-22752.

AMA Style

Hames MC, McFeeters H, Holloway WB, Stanley CB, Urban VS, McFeeters RL. Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA. International Journal of Molecular Sciences. 2013; 14(11):22741-22752.

Chicago/Turabian Style

Hames, Mary C.; McFeeters, Hana; Holloway, W. B.; Stanley, Christopher B.; Urban, Volker S.; McFeeters, Robert L. 2013. "Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA." Int. J. Mol. Sci. 14, no. 11: 22741-22752.

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert