The Structural and Molecular Mechanisms of Mycobacterium tuberculosis Translational Elongation Factor Proteins

Molecules. 2024 Apr 29;29(9):2058. doi: 10.3390/molecules29092058.

Abstract

Targeting translation factor proteins holds promise for developing innovative anti-tuberculosis drugs. During protein translation, many factors cause ribosomes to stall at messenger RNA (mRNA). To maintain protein homeostasis, bacteria have evolved various ribosome rescue mechanisms, including the predominant trans-translation process, to release stalled ribosomes and remove aberrant mRNAs. The rescue systems require the participation of translation elongation factor proteins (EFs) and are essential for bacterial physiology and reproduction. However, they disappear during eukaryotic evolution, which makes the essential proteins and translation elongation factors promising antimicrobial drug targets. Here, we review the structural and molecular mechanisms of the translation elongation factors EF-Tu, EF-Ts, and EF-G, which play essential roles in the normal translation and ribosome rescue mechanisms of Mycobacterium tuberculosis (Mtb). We also briefly describe the structure-based, computer-assisted study of anti-tuberculosis drugs.

Keywords: EF-G; EF-Ts; EF-Tu; Mycobacterium tuberculosis; molecular mechanism; structural; translation factor proteins.

Publication types

  • Review

MeSH terms

  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Models, Molecular
  • Mycobacterium tuberculosis* / drug effects
  • Mycobacterium tuberculosis* / genetics
  • Mycobacterium tuberculosis* / metabolism
  • Peptide Elongation Factors / chemistry
  • Peptide Elongation Factors / genetics
  • Peptide Elongation Factors / metabolism
  • Protein Biosynthesis
  • Protein Conformation
  • Ribosomes / metabolism
  • Tuberculosis / drug therapy
  • Tuberculosis / metabolism
  • Tuberculosis / microbiology

Substances

  • Bacterial Proteins
  • Peptide Elongation Factors
  • Antitubercular Agents