ACS Infectious Diseases p. 634 - 644 (2017)
Update date:2022-08-23
Topics:
Alumasa, John N.
Manzanillo, Paolo S.
Peterson, Nicholas D.
Lundrigan, Tricia
Baughn, Anthony D.
Cox, Jeffery S.
Keiler, Kenneth C.
The emergence of Mycobacterium tuberculosis (MTB) strains that are resistant to most or all available antibiotics has created a severe problem for treating tuberculosis and has spurred a quest for new antibiotic targets. Here, we demonstrate that trans-translation is essential for growth of MTB and is a viable target for development of antituberculosis drugs. We also show that an inhibitor of trans-translation, KKL-35, is bactericidal against MTB under both aerobic and anoxic conditions. Biochemical experiments show that this compound targets helix 89 of the 23S rRNA. In silico molecular docking predicts a binding pocket for KKL-35 adjacent to the peptidyl-transfer center in a region not targeted by conventional antibiotics. Computational solvent mapping suggests that this pocket is a druggable hot spot for small molecule binding. Collectively, our findings reveal a new target for antituberculosis drug development and provide critical insight on the mechanism of antibacterial action for KKL-35 and related 1,3,4-oxadiazole benzamides.
View MoreAnhui New Star Pharmaceutical Development Co., Ltd
Contact:013956922763
Address:Floor 3, F9A, F Workshop, No.110 Kexue Road, High-Tech Development Zone, Hefei, Anhui ,China
Shanghai Mintchem Development ., Ltd
Contact:0086 21 5190 8570
Address:R602,4#,89Nong, Mudan Road Pudong Shanghai China
qingdao goldenchem imp and exp co.,ltd.
Contact:532-55579246
Address:no.62 ,haier road laoshan distirct
BAODING SINO-CHEM INDUSTRY CO.,LTD
Contact:0312-5956088
Address:NO.8 FUXING ROAD,CHINA
website:http://www.win-winchemical.com
Contact:0086-577-64498589
Address:6F,No.396 Xingping Road,Longwan Industrial Zone
Doi:10.1002/chem.201403186
(2014)Doi:10.1021/ja210923k
(2012)Doi:10.1016/j.molstruc.2019.02.007
(2019)Doi:10.1007/BF01165727
(1996)Doi:10.1134/S107036321807006X
(2018)Doi:10.1016/j.tet.2016.09.015
(2016)