TY - JOUR
T1 - Small molecule binding, docking, and characterization of the interaction between Pth1 and peptidyl-tRNA
AU - Hames, Mary C.
AU - McFeeters, Hana
AU - Blake Holloway, W.
AU - Stanley, Christopher B.
AU - Urban, Volker S.
AU - McFeeters, Robert L.
PY - 2013/11/19
Y1 - 2013/11/19
N2 - 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.
AB - 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.
KW - Docking
KW - Enzyme-substrate complex
KW - Inhibition
KW - Peptidyl-tRNA hydrolase
KW - Small angle neutron scattering
UR - http://www.scopus.com/inward/record.url?scp=84887924167&partnerID=8YFLogxK
U2 - 10.3390/ijms141122741
DO - 10.3390/ijms141122741
M3 - Article
C2 - 24256814
AN - SCOPUS:84887924167
SN - 1661-6596
VL - 14
SP - 22741
EP - 22752
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 11
ER -
