Author/Editor | 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.; Roper, David I. | |
Title | Inhibition of D-Ala | |
Type | članek | |
Vol. and No. | , št. Vol. 8 | |
Publication year | 2017 | |
Volume | str. 1-7 | |
ISSN | 2041-1723 - Nature communications | |
Language | eng | |
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. | |
Descriptors | Farmacevtska kemija Kemoterapija | |
Keywords | D-cycloserine D-alanine ligase peptidoglycan biosynthesis enzymes nuclear physics experimental particle physics protons Compton scattering |