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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MDPI AG
2013-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/14/11/22741 |
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doaj-06d4c59a62d74e8496a8a62c1221ece52020-11-24T21:06:02ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-11-011411227412275210.3390/ijms141122741ijms141122741Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNAMary C. Hames0Hana McFeeters1W. Blake Holloway2Christopher B. Stanley3Volker S. Urban4Robert L. McFeeters5Department of Chemistry, University of Alabama in Huntsville, 301 Sparkman Drive, Huntsville, AL 35899, USADepartment of Chemistry, University of Alabama in Huntsville, 301 Sparkman Drive, Huntsville, AL 35899, USADepartment of Chemistry, University of Alabama in Huntsville, 301 Sparkman Drive, Huntsville, AL 35899, USAOak Ridge National Laboratory, Biology and Soft Matter Division, P.O. Box 2008, Oak Ridge, TN 37831, USAOak Ridge National Laboratory, Biology and Soft Matter Division, P.O. Box 2008, Oak Ridge, TN 37831, USADepartment of Chemistry, University of Alabama in Huntsville, 301 Sparkman Drive, Huntsville, AL 35899, USABacterial 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.http://www.mdpi.com/1422-0067/14/11/22741peptidyl-tRNA hydrolasesmall angle neutron scatteringenzyme-substrate complexdockinginhibition |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Mary C. Hames Hana McFeeters W. Blake Holloway Christopher B. Stanley Volker S. Urban Robert L. McFeeters |
| spellingShingle |
Mary C. Hames Hana McFeeters W. Blake Holloway Christopher B. Stanley Volker S. Urban Robert L. McFeeters Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA International Journal of Molecular Sciences peptidyl-tRNA hydrolase small angle neutron scattering enzyme-substrate complex docking inhibition |
| author_facet |
Mary C. Hames Hana McFeeters W. Blake Holloway Christopher B. Stanley Volker S. Urban Robert L. McFeeters |
| author_sort |
Mary C. Hames |
| title |
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_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_sort |
small molecule binding, docking, and characterization of the interaction between pth1 and peptidyl-trna |
| publisher |
MDPI AG |
| series |
International Journal of Molecular Sciences |
| issn |
1422-0067 |
| publishDate |
2013-11-01 |
| 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. |
| topic |
peptidyl-tRNA hydrolase small angle neutron scattering enzyme-substrate complex docking inhibition |
| url |
http://www.mdpi.com/1422-0067/14/11/22741 |
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