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