Skip Navigation



Nucleic Acids Research Advance Access published online on December 15, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm1088
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (2153K) Freely available
Right arrow Screen PDF (276K) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
36/2/697    most recent
gkm1088v1
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 Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Kawamoto, S. A.
Right arrow Articles by Gopalan, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kawamoto, S. A.
Right arrow Articles by Gopalan, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

RNA

Studies on the mechanism of inhibition of bacterial ribonuclease P by aminoglycoside derivatives

Steven A. Kawamoto, Christopher G. Sudhahar, Cynthia L. Hatfield, Jing Sun, Edward J. Behrman and Venkat Gopalan*

Department of Biochemistry, The Ohio State University, Columbus, OH 43210, USA

*To whom correspondence should be addressed. Tel: +1 614 292 1332; Fax: +1 614 292 6773; Email: gopalan.5{at}osu.edu

Received October 10, 2007. Revised November 19, 2007. Accepted November 20, 2007.

Ribonuclease P (RNase P) is a Mg2+-dependent endoribonuclease responsible for the 5'-maturation of transfer RNAs. It is a ribonucleoprotein complex containing an essential RNA and a varying number of protein subunits depending on the source: at least one, four and nine in Bacteria, Archaea and Eukarya, respectively. Since bacterial RNase P is required for viability and differs in structure/subunit composition from its eukaryal counterpart, it is a potential antibacterial target. To elucidate the basis for our previous finding that the hexa-arginine derivative of neomycin B is 500-fold more potent than neomycin B in inhibiting bacterial RNase P, we synthesized hexa-guanidinium and -lysyl conjugates of neomycin B and compared their inhibitory potential. Our studies indicate that side-chain length, flexibility and composition cumulatively account for the inhibitory potency of the aminoglycoside-arginine conjugates (AACs). We also demonstrate that AACs interfere with RNase P function by displacing Mg2+ ions. Moreover, our finding that an AAC can discriminate between a bacterial and archaeal (an experimental surrogate for eukaryal) RNase P holoenzyme lends promise to the design of aminoglycoside conjugates as selective inhibitors of bacterial RNase P, especially once the structural differences in RNase P from the three domains of life have been established.

The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.


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




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.