7VMX

The Crystal Structure of EF-Tu and EF-Ts complex from Mycobacterium tuberculosis

Summary for 7VMX

• Entry DOI: 10.2210/pdb7vmx/pdb
• Descriptor: Elongation factor Ts, Elongation factor Tu, ZINC ION, ... (5 entities in total)
• Functional Keywords: mycobacterium tuberculosis, elongation factor, protein translation, translation
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 2
• Total formula weight: 72860.92

Authors

Zhan, B.W.,Li, J.X. (deposition date: 2021-10-09, release date: 2022-10-12, Last modification date: 2024-04-24)

Primary citation

Zhan, B.,Gao, Y.,Gao, W.,Li, Y.,Li, Z.,Qi, Q.,Lan, X.,Shen, H.,Gan, J.,Zhao, G.,Li, J.
Structural insights of the elongation factor EF-Tu complexes in protein translation of Mycobacterium tuberculosis.
Commun Biol, 5:1052-1052, 2022

PubMed Abstract: Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the second-deadliest infectious disease worldwide. Emerging evidence shows that the elongation factor EF-Tu could be an excellent target for treating Mtb infection. Here, we report the crystal structures of Mtb EF-Tu•EF-Ts and EF-Tu•GDP complexes, showing the molecular basis of EF-Tu's representative recycling and inactive forms in protein translation. Mtb EF-Tu binds with EF-Ts at a 1:1 ratio in solution and crystal packing. Mutation and SAXS analysis show that EF-Ts residues Arg13, Asn82, and His149 are indispensable for the EF-Tu/EF-Ts complex formation. The GDP binding pocket of EF-Tu dramatically changes conformations upon binding with EF-Ts, sharing a similar GDP-exchange mechanism in E. coli and T. ther. Also, the FDA-approved drug Osimertinib inhibits the growth of M. smegmatis, H37Ra, and M. bovis BCG strains by directly binding with EF-Tu. Thus, our work reveals the structural basis of Mtb EF-Tu in polypeptide synthesis and may provide a promising candidate for TB treatment.

PubMed: 36192483
DOI: 10.1038/s42003-022-04019-y

Experimental method

X-RAY DIFFRACTION (2.8 Å)