Interactions of aminoglycoside antibiotics with rRNA

Biochem Soc Trans. 2016 Aug 15;44(4):987-93. doi: 10.1042/BST20160087.

Abstract

Aminoglycoside antibiotics are protein synthesis inhibitors applied to treat infections caused mainly by aerobic Gram-negative bacteria. Due to their adverse side effects they are last resort antibiotics typically used to combat pathogens resistant to other drugs. Aminoglycosides target ribosomes. We describe the interactions of aminoglycoside antibiotics containing a 2-deoxystreptamine (2-DOS) ring with 16S rRNA. We review the computational studies, with a focus on molecular dynamics (MD) simulations performed on RNA models mimicking the 2-DOS aminoglycoside binding site in the small ribosomal subunit. We also briefly discuss thermodynamics of interactions of these aminoglycosides with their 16S RNA target.

Keywords: MD simulations; aminoglycoside antibiotics; electrostatic interactions; molecular docking; rRNA; thermodynamics.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / chemistry*
  • Aminoglycosides / metabolism
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Binding Sites
  • Hexosamines / chemistry
  • Hexosamines / metabolism
  • Kinetics
  • Molecular Dynamics Simulation*
  • Molecular Structure
  • Nucleic Acid Conformation
  • RNA, Ribosomal, 16S / chemistry*
  • RNA, Ribosomal, 16S / metabolism
  • Thermodynamics

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Hexosamines
  • RNA, Ribosomal, 16S
  • 2-deoxystreptamine