Quinoline Derivatives Kill Mycobacterium tuberculosis by Activating Glutamate Kinase

Makafe, Gaelle G.1,5,6; Hussain, Muzammal1,2,6; Surineni, Goverdhan1,5,6; Tan, Yaoju3; Wong, Nai-Kei4; Julius, Mugweru1,9; Liu, Lanying1,5,6; Gift, Chiwala1,5,6; Jiang, Huofeng1,5,7; Tang, Yunxiang1,5,8; Liu, Jianxiong3; Tan, Shouyong3; Yu, Zhijun2,6; Liu, Zhiyong1,5; Lu, Zhili1,5; Fang, Cuiting1,5,6; Zhou, Yang10; Zhang, Jiancun1,2,6; Zhu, Qiang1,5,6; Liu, Jinsong1,2,5,6; Zhang, Tianyu1,5,6

2019-08-15

10.1016/j.chembiol.2019.05.003

Cell Chemical Biology   影响因子和分区

2451-9448

There is a great need for identification and development of new anti-tuberculosis drugs with novel targets. Recent drug-discovery efforts typically focus on identifying inhibitors but not activators that perturb metabolic enzymes' functions as a means to kill Mycobacterium tuberculosis (Mtb). Here, we describe a class of quinoline compounds, Z0933/Z0930, which kill Mtb by acting as activators of glutamate kinase (GK), a previously untargeted enzyme catalyzing the first step of proline biosynthesis. We further show that Z0933/Z0930 augment proline production and induce Mtb killing via proline-derived redox imbalance and production of reactive oxygen species. This work highlights the effectiveness of gain-of-function probes against Mtb and provides a framework for the discovery of next-generation allosteric activators of GK.

SCI

英语

其他

Science and Technology Innovation Leader of Guangdong Province[2016TX03R095]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000481604100015

CELL PRESS

Web of Science

1.Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China
2.Chinese Acad Sci, Guangdong Prov Key Lab Biocomp, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China
3.Guangzhou Chest Hosp, Dept Clin Lab, State Key Lab Resp Dis, 62 Hengzhigang Rd, Guangzhou 510095, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Hosp 2, Shenzhen Peoples Hosp 3, Key Discipline Infect Dis, 29 Bulan Rd, Shenzhen 518112, Peoples R China
5.Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China
6.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China
7.Univ Sci & Technol China, Sch Life Sci, 96 Jinzhai Rd, Hefei 230027, Anhui, Peoples R China
8.Anhui Univ, Inst Phys Sci & Informat Technol, 111 Jiulong Rd, Hefei 230009, Anhui, Peoples R China
9.Univ Embu, Dept Biol Sci, Embu 660100, Kenya
10.KTH Royal Inst Technol, Dept Theoret Chem & Biol, AlbaNova Univ Ctr, S-10691 Stockholm, Sweden

Makafe, Gaelle G.,Hussain, Muzammal,Surineni, Goverdhan,et al. Quinoline Derivatives Kill Mycobacterium tuberculosis by Activating Glutamate Kinase[J]. Cell Chemical Biology,2019,26(8):1187-+.

Makafe, Gaelle G..,Hussain, Muzammal.,Surineni, Goverdhan.,Tan, Yaoju.,Wong, Nai-Kei.,...&Zhang, Tianyu.(2019).Quinoline Derivatives Kill Mycobacterium tuberculosis by Activating Glutamate Kinase.Cell Chemical Biology,26(8),1187-+.

Makafe, Gaelle G.,et al."Quinoline Derivatives Kill Mycobacterium tuberculosis by Activating Glutamate Kinase".Cell Chemical Biology 26.8(2019):1187-+.