Skip Navigation



JAC Advance Access published online on February 22, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl556
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
59/4/640    most recent
dkl556v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Cheng, B.
Right arrow Articles by Tse-Dinh, Y.-C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cheng, B.
Right arrow Articles by Tse-Dinh, Y.-C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Compounds with antibacterial activity that enhance DNA cleavage by bacterial DNA topoisomerase I

Cheng Bokun, Liu I-Fen and Tse-Dinh Yuk-Ching*

Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA

Received 13 October 2006; returned 4 December 2006; revised 14 December 2006; accepted 21 December 2006

* Corresponding author. Tel: +1-914-594-4061; Fax: +1-914-594-4058; E-mail: yuk-ching_tse-dinh{at}nymc.edu

Objectives: DNA topoisomerases utilize a covalent complex formed after DNA cleavage as an intermediate in the interconversion of topological forms via DNA cleavage and religation. Many anticancer and antibacterial therapeutic agents are effective because they stabilize or increase the level of the covalent topoisomerase–DNA complex formed by type IIA or type IB topoisomerases. Our goal is to identify small molecules that can enhance DNA cleavage by type IA DNA topoisomerase. Compounds that act in this mechanism against type IA topoisomerase have not been identified previously and could be leads for development of a new class of antibacterial agents.

Methods: High throughput screening was carried out to select small molecules that induce the SOS response of Escherichia coli, overexpressing recombinant Yersinia pestis topoisomerase I. The initial hit compounds were further tested for inhibition of bacterial growth and bacterial topoisomerase I activity.

Results: Three compounds with antibacterial activity that enhance the cleavage activity of bacterial topoisomerase I were identified.

Conclusions: Small molecules that can enhance the DNA cleavage activity of type IA DNA topoisomerase can be identified and may provide leads for development of novel antibacterial compounds.

Key Words: antibiotics , high throughput screening , Y. pestis


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
Y.-C. Tse-Dinh
Bacterial topoisomerase I as a target for discovery of antibacterial compounds
Nucleic Acids Res., February 1, 2009; 37(3): 731 - 737.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
E. P. Sorokin, B. Cheng, S. Rathi, S. J. Aedo, M. V. Abrenica, and Y.-C. Tse-Dinh
Inhibition of Mg2+ binding and DNA religation by bacterial topoisomerase I via introduction of an additional positive charge into the active site region
Nucleic Acids Res., August 1, 2008; 36(14): 4788 - 4796.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
J. H. Sutherland, B. Cheng, I-F. Liu, and Y.-C. Tse-Dinh
SOS Induction by Stabilized Topoisomerase IA Cleavage Complex Occurs via the RecBCD Pathway
J. Bacteriol., May 1, 2008; 190(9): 3399 - 3403.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
B. Cheng, E. P. Sorokin, and Y.-C. Tse-Dinh
Mutation adjacent to the active site tyrosine can enhance DNA cleavage and cell killing by the TOPRIM Gly to Ser mutant of bacterial topoisomerase I
Nucleic Acids Res., February 11, 2008; 36(3): 1017 - 1025.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.