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 MoreTianjin Chemsyntech Chemical Co., Ltd
Contact:+86-22-60872258
Address:Haitai green industry base in Tianjin, K1,5-601
shandong zhongke taidou chemical co.,ltd
Contact:86-531-88682301
Address:Jinan shandong Province CHina
Guilin Zhenda Bio-Tech Co., Ltd.
Contact:86-773-3568977
Address:-Yangtang shangshui industry park, Lingui county,
Taixing Joxin Bio-tec Co.,Ltd.
website:http://www.joxbio.com
Contact:86-523-87558858 87612088
Address:No.88, chengdong industrial park
Contact:86-10-62983737; +86-10-51287608
Address:4/F Building C, 2 Shangdi Xinxi Road
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)