MurD enzymes from different bacteria: Evaluation of inhibitors
MurD enzymes from different bacteria: Evaluation of inhibitors
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DOI：
10.1016/j.bcp.2012.06.006
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发表时间：
2012-09-01
影响因子：
5.8
通讯作者：
Blanot, Didier
中科院分区：
文献类型：
--
作者：
Barreteau, Helene;Sosic, Izidor;Blanot, Didier
D-Glutamic acid-adding enzyme (MurD ligase) catalyses the addition of D-glutamic acid to UDP-N-acetylmuramoyl-L-alanine, an essential cytoplasmic step in the pathway for bacterial cell-wall peptidoglycan synthesis. As such, it represents an important antibacterial drug-discovery target enzyme. Recently, several series of compounds have been synthesised and found to inhibit MurD from Escherichia coli, the best one having an IC50 value of 8 mu M. In the present work, we have tested 20 of these compounds against the MurD enzymes from Staphylococcus aureus, Streptococcus pneumoniae, Borrelia burgdorferi and Mycobacterium tuberculosis. Most of the E. coli MurD inhibitors appeared less efficient against the four other orthologues. This divergent result can be explained by the differences in amino acid sequences and topologies of the active sites of the MurD ligases studied. (c) 2012 Elsevier Inc. All rights reserved.
