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

TITLE=Crystal Structure of Mycobacterium tuberculosis Elongation Factor G1

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.667638

DOI=10.3389/fmolb.2021.667638

ISSN=2296-889X

ABSTRACT=<p><italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) 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 <italic>Mtb</italic> is becoming a public health threat worldwide and makes the identification of anti-<italic>Mtb</italic> 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 <italic>Mtb</italic> 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.</p>