Conformational transition in the aminoacyl t-RNA site of the bacterial ribosome both in the presence and absence of an aminoglycoside antibiotic

Samy Meroueh, Shahriar Mobashery

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Peptide bonds are made at the ribosomal decoding site. Structural information reveals that two bases in the RNA that constitute the decoding site, A1492 and A1493, can have both intrahelical and extrahelical conformations. Aminoglycoside antibiotics bind to the decoding site, and the structural information reveals the two bases in the extrahelical positions. We have shown by explicit-solvent molecular dynamics simulations and free-energy calculations that ribosomal RNA bases A1492 and A1493 are inherently prone to sampling conformational states that include both intrahelical and extrahelical positions. The simulations reveal that base flipping occurs through the minor groove of the double helix. Furthermore, free-energy calculations for the conformational change of the bases to the extrahelical positions in both processes are exergonic and highly favorable. It is likely that the correct codon-anticodon recognition by mRNA and tRNA arrests the bases in extrahelical conformations in the course of normal translation. In contrast, the sequestration of the aminoglycoside antibiotic at the decoding site facilitates the conformational change of the bases to the extrahelical position. Once the antibiotic is bound, the extrahelical positions for the bases are highly favored based on contributions by both electrostatic and entropic components of the free energy for the process.

Original languageEnglish (US)
Pages (from-to)291-297
Number of pages7
JournalChemical Biology and Drug Design
Volume69
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Fingerprint

Bacterial RNA
Aminoglycosides
Ribosomes
Decoding
RNA
Free energy
Anti-Bacterial Agents
Anticodon
Conformations
Ribosomal RNA
Molecular Dynamics Simulation
Transfer RNA
Static Electricity
Codon
Molecular dynamics
Electrostatics
Messenger RNA
Peptides
Sampling
Computer simulation

Keywords

  • Antibiotic activity
  • Conformational change
  • Ribosome

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

@article{aed01b5c6f9148038898e60f6f45d455,
title = "Conformational transition in the aminoacyl t-RNA site of the bacterial ribosome both in the presence and absence of an aminoglycoside antibiotic",
abstract = "Peptide bonds are made at the ribosomal decoding site. Structural information reveals that two bases in the RNA that constitute the decoding site, A1492 and A1493, can have both intrahelical and extrahelical conformations. Aminoglycoside antibiotics bind to the decoding site, and the structural information reveals the two bases in the extrahelical positions. We have shown by explicit-solvent molecular dynamics simulations and free-energy calculations that ribosomal RNA bases A1492 and A1493 are inherently prone to sampling conformational states that include both intrahelical and extrahelical positions. The simulations reveal that base flipping occurs through the minor groove of the double helix. Furthermore, free-energy calculations for the conformational change of the bases to the extrahelical positions in both processes are exergonic and highly favorable. It is likely that the correct codon-anticodon recognition by mRNA and tRNA arrests the bases in extrahelical conformations in the course of normal translation. In contrast, the sequestration of the aminoglycoside antibiotic at the decoding site facilitates the conformational change of the bases to the extrahelical position. Once the antibiotic is bound, the extrahelical positions for the bases are highly favored based on contributions by both electrostatic and entropic components of the free energy for the process.",
keywords = "Antibiotic activity, Conformational change, Ribosome",
author = "Samy Meroueh and Shahriar Mobashery",
year = "2007",
month = "5",
doi = "10.1111/j.1747-0285.2007.00505.x",
language = "English (US)",
volume = "69",
pages = "291--297",
journal = "Chemical Biology and Drug Design",
issn = "1747-0277",
publisher = "Blackwell",
number = "5",

}

TY - JOUR

T1 - Conformational transition in the aminoacyl t-RNA site of the bacterial ribosome both in the presence and absence of an aminoglycoside antibiotic

AU - Meroueh, Samy

AU - Mobashery, Shahriar

PY - 2007/5

Y1 - 2007/5

N2 - Peptide bonds are made at the ribosomal decoding site. Structural information reveals that two bases in the RNA that constitute the decoding site, A1492 and A1493, can have both intrahelical and extrahelical conformations. Aminoglycoside antibiotics bind to the decoding site, and the structural information reveals the two bases in the extrahelical positions. We have shown by explicit-solvent molecular dynamics simulations and free-energy calculations that ribosomal RNA bases A1492 and A1493 are inherently prone to sampling conformational states that include both intrahelical and extrahelical positions. The simulations reveal that base flipping occurs through the minor groove of the double helix. Furthermore, free-energy calculations for the conformational change of the bases to the extrahelical positions in both processes are exergonic and highly favorable. It is likely that the correct codon-anticodon recognition by mRNA and tRNA arrests the bases in extrahelical conformations in the course of normal translation. In contrast, the sequestration of the aminoglycoside antibiotic at the decoding site facilitates the conformational change of the bases to the extrahelical position. Once the antibiotic is bound, the extrahelical positions for the bases are highly favored based on contributions by both electrostatic and entropic components of the free energy for the process.

AB - Peptide bonds are made at the ribosomal decoding site. Structural information reveals that two bases in the RNA that constitute the decoding site, A1492 and A1493, can have both intrahelical and extrahelical conformations. Aminoglycoside antibiotics bind to the decoding site, and the structural information reveals the two bases in the extrahelical positions. We have shown by explicit-solvent molecular dynamics simulations and free-energy calculations that ribosomal RNA bases A1492 and A1493 are inherently prone to sampling conformational states that include both intrahelical and extrahelical positions. The simulations reveal that base flipping occurs through the minor groove of the double helix. Furthermore, free-energy calculations for the conformational change of the bases to the extrahelical positions in both processes are exergonic and highly favorable. It is likely that the correct codon-anticodon recognition by mRNA and tRNA arrests the bases in extrahelical conformations in the course of normal translation. In contrast, the sequestration of the aminoglycoside antibiotic at the decoding site facilitates the conformational change of the bases to the extrahelical position. Once the antibiotic is bound, the extrahelical positions for the bases are highly favored based on contributions by both electrostatic and entropic components of the free energy for the process.

KW - Antibiotic activity

KW - Conformational change

KW - Ribosome

UR - http://www.scopus.com/inward/record.url?scp=34249277111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249277111&partnerID=8YFLogxK

U2 - 10.1111/j.1747-0285.2007.00505.x

DO - 10.1111/j.1747-0285.2007.00505.x

M3 - Article

VL - 69

SP - 291

EP - 297

JO - Chemical Biology and Drug Design

JF - Chemical Biology and Drug Design

SN - 1747-0277

IS - 5

ER -