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

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...

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Detalles Bibliográficos
Autores principales: Hames, Mary C., McFeeters, Hana, Holloway, W. Blake, Stanley, Christopher B., Urban, Volker S., McFeeters, Robert L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856088/
https://www.ncbi.nlm.nih.gov/pubmed/24256814
http://dx.doi.org/10.3390/ijms141122741
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author Hames, Mary C.
McFeeters, Hana
Holloway, W. Blake
Stanley, Christopher B.
Urban, Volker S.
McFeeters, Robert L.
author_facet Hames, Mary C.
McFeeters, Hana
Holloway, W. Blake
Stanley, Christopher B.
Urban, Volker S.
McFeeters, Robert L.
author_sort Hames, Mary C.
collection PubMed
description 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.
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spelling pubmed-38560882013-12-09 Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA Hames, Mary C. McFeeters, Hana Holloway, W. Blake Stanley, Christopher B. Urban, Volker S. McFeeters, Robert L. Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2013-11-19 /pmc/articles/PMC3856088/ /pubmed/24256814 http://dx.doi.org/10.3390/ijms141122741 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Hames, Mary C.
McFeeters, Hana
Holloway, W. Blake
Stanley, Christopher B.
Urban, Volker S.
McFeeters, Robert L.
Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA
title Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA
title_full Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA
title_fullStr Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA
title_full_unstemmed Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA
title_short Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA
title_sort small molecule binding, docking, and characterization of the interaction between pth1 and peptidyl-trna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856088/
https://www.ncbi.nlm.nih.gov/pubmed/24256814
http://dx.doi.org/10.3390/ijms141122741
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