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Quinoline Derivatives Kill Mycobacterium tuberculosis by Activating Glutamate Kinase

Makafe, Gaelle G. (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
Hussain, Muzammal (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Chinese Acad Sci, Guangdong Prov Key Lab Biocomp, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
Surineni, Goverdhan (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
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Tan, Yaoju (author)
Guangzhou Chest Hosp, Dept Clin Lab, State Key Lab Resp Dis, 62 Hengzhigang Rd, Guangzhou 510095, Guangdong, Peoples R China.
Wong, Nai-Kei (author)
Southern Univ Sci & Technol, Hosp 2, Shenzhen Peoples Hosp 3, Key Discipline Infect Dis, 29 Bulan Rd, Shenzhen 518112, Peoples R China.
Julius, Mugweru (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Embu, Dept Biol Sci, Embu 660100, Kenya.
Liu, Lanying (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
Gift, Chiwala (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
Jiang, Huofeng (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Sci & Technol China, Sch Life Sci, 96 Jinzhai Rd, Hefei 230027, Anhui, Peoples R China.
Tang, Yunxiang (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Anhui Univ, Inst Phys Sci & Informat Technol, 111 Jiulong Rd, Hefei 230009, Anhui, Peoples R China.
Liu, Jianxiong (author)
Guangzhou Chest Hosp, Dept Clin Lab, State Key Lab Resp Dis, 62 Hengzhigang Rd, Guangzhou 510095, Guangdong, Peoples R China.
Tan, Shouyong (author)
Guangzhou Chest Hosp, Dept Clin Lab, State Key Lab Resp Dis, 62 Hengzhigang Rd, Guangzhou 510095, Guangdong, Peoples R China.
Yu, Zhijun (author)
Chinese Acad Sci, Guangdong Prov Key Lab Biocomp, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
Liu, Zhiyong (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.
Lu, Zhili (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.
Fang, Cuiting (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
Zhou, Yang, 1986- (author)
KTH,Teoretisk kemi och biologi
Zhang, Jiancun (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Chinese Acad Sci, Guangdong Prov Key Lab Biocomp, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
Zhu, Qiang (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
Liu, Jinsong (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Chinese Acad Sci, Guangdong Prov Key Lab Biocomp, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
Zhang, Tianyu (author)
Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China.
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Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China;Guangzhou Regenerat Med & Hlth Guangdong Lab GRM, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China. Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Chinese Acad Sci, Guangdong Prov Key Lab Biocomp, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Sci Pk, Guangzhou 510530, Guangdong, Peoples R China.;Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China. (creator_code:org_t)
CELL PRESS, 2019
2019
English.
In: Cell Chemical Biology. - : CELL PRESS. - 2451-9456 .- 2451-9448. ; 26:8, s. 1187-
Related links:
http://www.cell.com/...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

NATURVETENSKAP  -- Kemi -- Teoretisk kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences -- Theoretical Chemistry (hsv//eng)

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art (subject category)

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