English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Mechanism of Tet(O)-mediated tetracycline resistance

Connell, S. R., Trieber, C. A., Dinos, G. P., Einfeldt, E., Taylor, D. E., & Nierhaus, K. H. (2003). Mechanism of Tet(O)-mediated tetracycline resistance. EMBO Journal, 22(4), 945-953.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8AB0-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8AB1-F
Genre: Journal Article
Alternative Title : Embo J.

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Connell, Sean R.1, Author              
Trieber, Catharine A., Author
Dinos, George P., Author
Einfeldt, Edda2, Author              
Taylor, Diane E., Author
Nierhaus, Knud H.3, Author              
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
2Mechanisms of Transcriptional Regulation (Sebastiaan H. Meijsing), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479641              
3Ribosomes, Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433558              

Content

show
hide
Free keywords: antibiotic resistance; protein synthesis; ribosome; Tet(O); tetracycline
 Abstract: Tet(O) is an elongation factor-like protein which confers resistance to the protein synthesis inhibitor tetracycline by promoting the release of the drug from its inhibitory site on the ribosome. Here we investigated the interaction of Tet(O) with the elongating ribosome and show, using dimethyl sulfate (DMS) probing and binding assays, that it interacts preferentially with the post-translocational ribosome. Furthermore, using an XTP-dependent mutant of Tet(O), we demonstrated that Tet(O) induces conformational rearrangements within the ribosome which can be detected by EF-Tu, and manifested as a stimulation in the GTPase activity of this elongation factor. As such, these conformational changes probably involve the ribosomal GTPase-associated center and, accordingly, Tet(O) alters the DMS modification pattern of the L11 region. Additionally, tetracycline binding is associated with an Ea of 58 kJ/mol. These results suggest a model where both Tet(O) and tetracycline induce a conformational change in functionally opposite directions and the Tet(O)-induced conformation persists after it has left the ribosome; this prevents rebinding of the drug while allowing productive A-site occupation by a ternary complex in the presence of tetracycline.

Details

show
hide
Language(s): eng - English
 Dates: 2003-02-17
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 174937
ISI: 000181280100019
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: EMBO Journal
  Alternative Title : Embo J.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 22 (4) Sequence Number: - Start / End Page: 945 - 953 Identifier: ISSN: 0261-4189