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

International Journal of Molecular Sciences

Mary C. Hames¹  Hana McFeeters¹  W. Blake Holloway¹  Christopher B. Stanley²  Volker S. Urban² 

[1] Department of Chemistry, University of Alabama in Huntsville, 301 Sparkman Drive, Huntsville, AL 35899, USA; E-Mails:;Oak Ridge National Laboratory, Biology and Soft Matter Division, P.O. Box 2008, Oak Ridge, TN 37831, USA; E-Mails:

关键词: peptidyl-tRNA hydrolase;    small angle neutron scattering;    enzyme-substrate complex;    docking;    inhibition;   

DOI  :  10.3390/ijms141122741

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland