Skip Navigation

Nucleic Acids Research 2005 33(10):3085-3094; doi:10.1093/nar/gki622
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (1599K) Freely available
Right arrow Screen PDF (483K) Freely available
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 ISI Web of Science
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 Search for citing articles in:
ISI Web of Science (3)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Manjunatha, U. H.
Right arrow Articles by Nagaraja, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Manjunatha, U. H.
Right arrow Articles by Nagaraja, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published online 1 June 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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{at}oupjournals.org

Article

A monoclonal antibody that inhibits mycobacterial DNA gyrase by a novel mechanism

Ujjini H. Manjunatha, Anthony Maxwell1 and Valakunja Nagaraja*

Department of Microbiology and Cell Biology, Indian Institute of Science Bangalore, 560 012, India 1Department of Biological Chemistry, John Innes Centre Norwich Research Park, Colney, Norwich NR4 7UH, UK

*To whom correspondence should be addressed. Tel: +91 80 2360 0668; Fax: +91 80 2360 2697; Email: vraj{at}mcbl.iisc.ernet.in

Received March 15, 2005. Revised May 10, 2005. Accepted May 10, 2005.

DNA gyrase is a DNA topoisomerase indispensable for cellular functions in bacteria. We describe a novel, hitherto unknown, mechanism of specific inhibition of Mycobacterium smegmatis and Mycobacterium tuberculosis DNA gyrase by a monoclonal antibody (mAb). Binding of the mAb did not affect either GyrA–GyrB or gyrase–DNA interactions. More importantly, the ternary complex of gyrase–DNA–mAb retained the ATPase activity of the enzyme and was competent to catalyse DNA cleavage–religation reactions, implying a new mode of action different from other classes of gyrase inhibitors. DNA gyrase purified from fluoroquinolone-resistant strains of M.tuberculosis and M.smegmatis were inhibited by the mAb. The absence of cross-resistance of the drug-resistant enzymes from two different sources to the antibody-mediated inhibition corroborates the new mechanism of inhibition. We suggest that binding of the mAb in the proximity of the primary dimer interface region of GyrA in the heterotetrameric enzyme appears to block the release of the transported segment after strand passage, leading to enzyme inhibition. The specific inhibition of mycobacterial DNA gyrase with the mAb opens up new avenues for designing novel lead molecules for drug discovery and for probing gyrase mechanism.

Present address: Ujjini H. Manjunatha, Tuberculosis Research Section, NIAID, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA


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
S. Sengupta, M. Shah, and V. Nagaraja
Glutamate racemase from Mycobacterium tuberculosis inhibits DNA gyrase by affecting its DNA-binding
Nucleic Acids Res., November 14, 2006; 34(19): 5567 - 5576.
[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.