Inhibition of D-Ala : D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine
| العنوان: | Inhibition of D-Ala : D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine |
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| المؤلفون: | Dean Rea, Christopher W. Thoroughgood, Luiz Pedro S. de Carvalho, S. Batson, Cesira de Chiara, Vita Majce, David I. Roper, Vilmos Fülöp, Colin W. G. Fishwick, Katie J. Simmons, Christopher G. Dowson, Stanislav Gobec, Adrian J. Lloyd |
| المصدر: | Nature Communications, Vol 8, Iss 1, Pp 1-7 (2017) Nature Communications |
| بيانات النشر: | Nature Publishing Group, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Science, D-cycloserine, General Physics and Astronomy, chemical and pharmacologic phenomena, General Biochemistry, Genetics and Molecular Biology, Bacterial cell structure, Article, 03 medical and health sciences, Alanine racemase, medicine, Escherichia coli, Peptide Synthases, Phosphorylation, lcsh:Science, Antibiotics, Antitubercular, chemistry.chemical_classification, DNA ligase, Multidisciplinary, 030102 biochemistry & molecular biology, Escherichia coli Proteins, Cycloserine, Alanine Racemase, hemic and immune systems, General Chemistry, 3. Good health, QR, carbohydrates (lipids), 030104 developmental biology, Enzyme, chemistry, Biochemistry, Mechanism of action, lcsh:Q, medicine.symptom, medicine.drug |
| الوصف: | 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. The antibiotic D-cycloserine (DCS) targets the peptidoglycan biosynthesis enzyme D-Ala-D-Ala ligase (Ddl). Here the authors reveal the DCS inhibitory mechanism by determining the structure of E. coli DdlB with a phosphorylated DCS molecule in the active site that formed in crystallo and mimics the D-alanyl phosphate intermediate. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bb8c3d91c18a7a14bfd843d766186dd0 http://wrap.warwick.ac.uk/95976/1/WRAP-inhibition-D-Ala-D-Ala-ligase-phosphorylated-antibiotic-Roper-2017.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bb8c3d91c18a7a14bfd843d766186dd0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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