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Inhibition of D-Ala : D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine
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Batson, Sarah, de Chiara, Cesira, Majce, Vita, Lloyd, Adrian J., Gobec, Stanislav, Rea, Dean, Fülöp, Vilmos, Thoroughgood, Christopher W., Simmons, Katie J., Dowson, Christopher G., Fishwick, Colin W. G., de Carvalho, Luiz Pedro S. and Roper, David I. (2017) Inhibition of D-Ala : D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine. Nature Communications, 8 (1). 1939 . doi:10.1038/s41467-017-02118-7
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WRAP-inhibition-D-Ala-D-Ala-ligase-phosphorylated-antibiotic-Roper-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1277Kb) | Preview |
Official URL: http://dx.doi.org/10.1038/s41467-017-02118-7
Abstract
D-cycloserine is an antibiotic which targets sequential bacterial cell wall peptidoglycan biosynthesis enzymes: alanine racemase and D-alanine:D-alanine ligase. By a combination of structural, chemical and mechanistic studies here we show that the inhibition of D-alanine:D-alanine ligase by the antibiotic D-cycloserine proceeds via a distinct phosphorylated form of the drug. This mechanistic insight reveals a bimodal mechanism of action for a single antibiotic on different enzyme targets and has significance for the design of future inhibitor molecules based on this chemical structure.
| Item Type: | Journal Article | |||||||||||||||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QR Microbiology | |||||||||||||||||||||||||||||||||||||||||||||
| Divisions: | Faculty of Science > Life Sciences (2010- ) | |||||||||||||||||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Alanine -- Synthesis -- Inhibitors, Antibiotics | |||||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Nature Communications | |||||||||||||||||||||||||||||||||||||||||||||
| Publisher: | Nature Publishing Group | |||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 2041-1723 | |||||||||||||||||||||||||||||||||||||||||||||
| Official Date: | 5 December 2017 | |||||||||||||||||||||||||||||||||||||||||||||
| Dates: |
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| Date of first compliant deposit: | 6 December 2017 | |||||||||||||||||||||||||||||||||||||||||||||
| Volume: | 8 | |||||||||||||||||||||||||||||||||||||||||||||
| Number: | 1 | |||||||||||||||||||||||||||||||||||||||||||||
| Article Number: | 1939 | |||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1038/s41467-017-02118-7 | |||||||||||||||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||||||||||||||||||||
| Access rights to Published version: | Open Access | |||||||||||||||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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