Structure-based design of anti-mycobacterial drug leads that target the mycolic acid transporter MmpL3

doi:10.1016/j.str.2022.07.009

	Structure-based design of anti-mycobacterial drug leads that target the mycolic acid transporter MmpL3
	Hu, Tianyu1,2,7,8 ; Yang, Xiaolin1,2 ; Liu, Fengjiang 3; Sun, Shan1,2 ; Xiong, Zhiqi 4; Liang, Jingxi 5; Yang, Xiaobao1,2 ; Wang, Haofeng1,2 ; Yang, Xiuna1,2,9 ; Guddat, Luke W.6; Yang, Haitao1,2,9 ; Rao, Zihe1,2,3,4,5,9 ; Zhang, Bing1,2,9
	2022-10-06
发表期刊	STRUCTURE (IF:4.4[JCR-2023],4.3[5-Year])
ISSN	0969-2126
EISSN	1878-4186
卷号	30 期号:10 页码:1395-+
DOI	10.1016/j.str.2022.07.009
摘要	New anti-tubercular agents are urgently needed to address the emerging threat of drug resistance to human tuberculosis. Here, we have used structure-assisted methods to develop compounds that target mycobac-terial membrane protein large 3 (MmpL3). MmpL3 is essential for the transport of mycolic acids, an important cell-wall component of mycobacteria. We prepared compounds that potently inhibit the growth of Mycobac-terium tuberculosis (Mtb) and other mycobacteria in cell culture. The cryoelectron microscopy (cryo-EM) structure of mycobacterial MmpL3 in complex with one of these compounds (ST004) was determined using lipid nanodiscs at an overall resolution of 3.36 A. The structure reveals the binding mode of ST004 to MmpL3, with the S4 and S5 subsites of the inhibitor-binding pocket in the proton translocation channel playing vital roles. These data are a promising starting point for the development of anti-tuberculosis drugs that target MmpL3.
收录类别	SCIE
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS记录号	WOS:000872396900005
出版者	CELL PRESS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/243347
专题	生命科学与技术学院_博士生免疫化学研究所_特聘教授组_抗体化学实验室免疫化学研究所_特聘教授组_饶子和组免疫化学研究所_PI研究组_杨海涛组
通讯作者	Yang, Haitao; Rao, Zihe; Zhang, Bing
作者单位	1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 3.Guangzhou Lab, Innovat Ctr Pathogen Res, Guangzhou 510005, Peoples R China; 4.Tsinghua Univ, Lab Struct Biol, Beijing 100084, Peoples R China; 5.Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300353, Peoples R China; 6.Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia; 7.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China; 8.Univ Chinese Acad Sci, Beijing 100101, Peoples R China; 9.Shanghai Clin Res & Trial Ctr, Shanghai 201210, Peoples R China
第一作者单位	免疫化学研究所; 生命科学与技术学院
通讯作者单位	免疫化学研究所; 生命科学与技术学院
第一作者的第一单位	免疫化学研究所
推荐引用方式 GB/T 7714	Hu, Tianyu,Yang, Xiaolin,Liu, Fengjiang,et al. Structure-based design of anti-mycobacterial drug leads that target the mycolic acid transporter MmpL3[J]. STRUCTURE,2022,30(10):1395-+.
APA	Hu, Tianyu.,Yang, Xiaolin.,Liu, Fengjiang.,Sun, Shan.,Xiong, Zhiqi.,...&Zhang, Bing.(2022).Structure-based design of anti-mycobacterial drug leads that target the mycolic acid transporter MmpL3.STRUCTURE,30(10),1395-+.
MLA	Hu, Tianyu,et al."Structure-based design of anti-mycobacterial drug leads that target the mycolic acid transporter MmpL3".STRUCTURE 30.10(2022):1395-+.