Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site

JB Murray; SO Meroueh; Rupert James Martin Russell; G Lentzen; J Haddad; S Mobashery

doi:10.1016/j.chembiol.2005.11.004

Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site

JB Murray, SO Meroueh, Rupert James Martin Russell, G Lentzen, J Haddad, S Mobashery

Research output: Contribution to journal › Article › peer-review

Abstract

The X-ray crystal structures for the complexes of three designer antibiotics, compounds 1, 2, and 3, bound to two models for the ribosomal aminoacyl-tRNA site (A site) at 2.5-3.0 angstrom resolution and that of neamine at 2.8 angstrom resolution are described. Furthermore, the complex of antibiotic 1 bound to the A site in the entire 30S ribosomal subunit of Thermus thermophilus is reported at 3.8 angstrom resolution. Molecular dynamics simulations revealed that the designer compounds provide additional stability to bases A1492 and A1493 in their extrahelical forms. Snapshots from the simulations were used for free energy calculations, which revealed that van der Waals and hydrophobic effects were the driving forces behind the binding of designer antibiotic 3 when compared to the parental neamine.

Original language	English
Pages (from-to)	129-138
Number of pages	10
Journal	Chemistry and Biology
Volume	13
DOIs	https://doi.org/10.1016/j.chembiol.2005.11.004
Publication status	Published - Feb 2006

Keywords

CONTINUUM SOLVENT
CRYSTAL-STRUCTURE
SUBUNIT
RECOGNITION
BINDING
CRYSTALLOGRAPHY
TRANSLATION
SYSTEMS
MODEL
DNA

Access to Document

10.1016/j.chembiol.2005.11.004

Cite this

@article{34399abf85fa402083a716ac3a98f4ff,

title = "Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site",

abstract = "The X-ray crystal structures for the complexes of three designer antibiotics, compounds 1, 2, and 3, bound to two models for the ribosomal aminoacyl-tRNA site (A site) at 2.5-3.0 angstrom resolution and that of neamine at 2.8 angstrom resolution are described. Furthermore, the complex of antibiotic 1 bound to the A site in the entire 30S ribosomal subunit of Thermus thermophilus is reported at 3.8 angstrom resolution. Molecular dynamics simulations revealed that the designer compounds provide additional stability to bases A1492 and A1493 in their extrahelical forms. Snapshots from the simulations were used for free energy calculations, which revealed that van der Waals and hydrophobic effects were the driving forces behind the binding of designer antibiotic 3 when compared to the parental neamine.",

keywords = "CONTINUUM SOLVENT, CRYSTAL-STRUCTURE, SUBUNIT, RECOGNITION, BINDING, CRYSTALLOGRAPHY, TRANSLATION, SYSTEMS, MODEL, DNA",

author = "JB Murray and SO Meroueh and Russell, {Rupert James Martin} and G Lentzen and J Haddad and S Mobashery",

year = "2006",

month = feb,

doi = "10.1016/j.chembiol.2005.11.004",

language = "English",

volume = "13",

pages = "129--138",

journal = "Chemistry and Biology",

publisher = "Cell Press",

}

TY - JOUR

T1 - Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site

AU - Murray, JB

AU - Meroueh, SO

AU - Russell, Rupert James Martin

AU - Lentzen, G

AU - Haddad, J

AU - Mobashery, S

PY - 2006/2

Y1 - 2006/2

N2 - The X-ray crystal structures for the complexes of three designer antibiotics, compounds 1, 2, and 3, bound to two models for the ribosomal aminoacyl-tRNA site (A site) at 2.5-3.0 angstrom resolution and that of neamine at 2.8 angstrom resolution are described. Furthermore, the complex of antibiotic 1 bound to the A site in the entire 30S ribosomal subunit of Thermus thermophilus is reported at 3.8 angstrom resolution. Molecular dynamics simulations revealed that the designer compounds provide additional stability to bases A1492 and A1493 in their extrahelical forms. Snapshots from the simulations were used for free energy calculations, which revealed that van der Waals and hydrophobic effects were the driving forces behind the binding of designer antibiotic 3 when compared to the parental neamine.

AB - The X-ray crystal structures for the complexes of three designer antibiotics, compounds 1, 2, and 3, bound to two models for the ribosomal aminoacyl-tRNA site (A site) at 2.5-3.0 angstrom resolution and that of neamine at 2.8 angstrom resolution are described. Furthermore, the complex of antibiotic 1 bound to the A site in the entire 30S ribosomal subunit of Thermus thermophilus is reported at 3.8 angstrom resolution. Molecular dynamics simulations revealed that the designer compounds provide additional stability to bases A1492 and A1493 in their extrahelical forms. Snapshots from the simulations were used for free energy calculations, which revealed that van der Waals and hydrophobic effects were the driving forces behind the binding of designer antibiotic 3 when compared to the parental neamine.

KW - CONTINUUM SOLVENT

KW - CRYSTAL-STRUCTURE

KW - SUBUNIT

KW - RECOGNITION

KW - BINDING

KW - CRYSTALLOGRAPHY

KW - TRANSLATION

KW - SYSTEMS

KW - MODEL

KW - DNA

UR - http://www.scopus.com/inward/record.url?scp=32844459761&partnerID=8YFLogxK

U2 - 10.1016/j.chembiol.2005.11.004

DO - 10.1016/j.chembiol.2005.11.004

M3 - Article

VL - 13

SP - 129

EP - 138

JO - Chemistry and Biology

JF - Chemistry and Biology

ER -

Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this