Crystal Structure of Mycobacterium tuberculosis Elongation Factor G1

Gao, Xiaopan1,2; Yu, Xia1,2,3; Zhu, Kaixiang1,2; Qin, Bo1,2; Wang, Wei1,2; Han, Pu4; Wojdyla, Justyna Aleksandra5; Wang, Meitian5; Cui, Sheng1,2,6

2021-09-03

10.3389/fmolb.2021.667638

FRONTIERS IN MOLECULAR BIOSCIENCES   影响因子和分区

2296-889X

Mycobacterium tuberculosis (Mtb) caused an estimated 10 million cases of tuberculosis and 1.2 million deaths in 2019 globally. The increasing emergence of multidrug-resistant and extensively drug-resistant Mtb is becoming a public health threat worldwide and makes the identification of anti-Mtb drug targets urgent. Elongation factor G (EF-G) is involved in tRNA translocation on ribosomes during protein translation. Therefore, EF-G is a major focus of structural analysis and a valuable drug target of antibiotics. However, the crystal structure of Mtb EF-G1 is not yet available, and this has limited the design of inhibitors. Here, we report the crystal structure of Mtb EF-G1 in complex with GDP. The unique crystal form of the Mtb EF-G1-GDP complex provides an excellent platform for fragment-based screening using a crystallographic approach. Our findings provide a structure-based explanation for GDP recognition, and facilitate the identification of EF-G1 inhibitors with potential interest in the context of drug discovery.

Mycobacteria tuberculosis Elongatin factor G (EF-G) crystal structure antituberculosis drug ribosome-bound EF-G

SCI

英语

通讯

National Natural Science Foundation of China[81971985,82072291,81772207,11775308,81802057] ; Chinese Academy of Medical Science (CAMS) Innovation Fund for Medical Sciences[2016-I2M-1-013,2017-I2M-1-014] ; National Key Research and Development Program of China["2016YFD0500300","2019YFC0840602"] ; Beijing Municipal Natural Science Foundation[7182117,7174288] ; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences["2018PT51009","2017PT31049"] ; Guangdong Foundation for Basic and Applied Basic Research[2019B1515120041]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000696553800001

FRONTIERS MEDIA SA

Web of Science

1.Chinese Acad Med Sci & Peking Union Med Coll, Inst Pathogen Biol, NHC Key Lab Syst Biol Pathogens, Beijing, Peoples R China
2.Chinese Acad Med Sci & Peking Union Med Coll, Ctr TB Res, Beijing, Peoples R China
3.Capital Med Univ, Beijing TB & Thorac Tumor Inst, Beijing Chest Hosp, Beijing Key Lab Drug Resistant TB Res,Natl Clin L, Beijing, Peoples R China
4.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China
5.Paul Scherrer Inst, Swiss Light Source, Villigen, Switzerland
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis, Sanming Project Med Shenzhen Construct Novel Syst, Shenzhen, Peoples R China

Gao, Xiaopan,Yu, Xia,Zhu, Kaixiang,et al. Crystal Structure of Mycobacterium tuberculosis Elongation Factor G1[J]. FRONTIERS IN MOLECULAR BIOSCIENCES,2021,8.

Gao, Xiaopan.,Yu, Xia.,Zhu, Kaixiang.,Qin, Bo.,Wang, Wei.,...&Cui, Sheng.(2021).Crystal Structure of Mycobacterium tuberculosis Elongation Factor G1.FRONTIERS IN MOLECULAR BIOSCIENCES,8.

Gao, Xiaopan,et al."Crystal Structure of Mycobacterium tuberculosis Elongation Factor G1".FRONTIERS IN MOLECULAR BIOSCIENCES 8(2021).