Crystal Structure of Mycobacterium tuberculosis Elongation Factor G1

Xiaopan Gao; Xia Yu; Kaixiang Zhu; Bo Qin; Wei Wang; Pu Han; Justyna Aleksandra Wojdyla; Meitian Wang; Sheng Cui

doi:10.3389/fmolb.2021.667638

Crystal Structure of Mycobacterium tuberculosis Elongation Factor G1

Front Mol Biosci. 2021 Sep 3:8:667638. doi: 10.3389/fmolb.2021.667638. eCollection 2021.

Authors

Xiaopan Gao¹, Xia Yu^{1

2}, Kaixiang Zhu¹, Bo Qin¹, Wei Wang¹, Pu Han³, Justyna Aleksandra Wojdyla⁴, Meitian Wang⁴, Sheng Cui^{1

5}

Affiliations

¹ NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, And Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-resistant Tuberculosis Research Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Institute, Capital Medical University, Beijing, China.
³ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁴ Swiss Light Source at the Paul Scherrer Institut, Villigen, Switzerland.
⁵ Sanming Project of Medicine in Shenzhen on Construction of Novel Systematic Network Against Tuberculosis, National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China.

Abstract

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.

Keywords: Elongatin factor G (EF-G); Mycobacteria tuberculosis; antituberculosis drug; crystal structure; ribosome-bound EF-G.