Skip Navigation



Nucleic Acids Research Advance Access published online on September 18, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp669
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (2099K) Freely available
Right arrow Screen PDF (1136K) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
37/20/6849    most recent
gkp669v1
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 Fiorani, P.
Right arrow Articles by Desideri, A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fiorani, P.
Right arrow Articles by Desideri, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nucleic Acid Enzymes

Evidence of the crucial role of the linker domain on the catalytic activity of human topoisomerase I by experimental and simulative characterization of the Lys681Ala mutant

Paola Fiorani1, Cinzia Tesauro1, Giordano Mancini2, Giovanni Chillemi2, Ilda D'A;nnessa1,2, Grazia Graziani3, Lucio Tentori3, Alessia Muzi3 and Alessandro Desideri1,*

1CNR National Research Council, INFM National Institute for the Physics of Matter and Department of Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome 00133, 2CASPUR Interuniversities Consortium for Supercomputing Applications, Via dei Tizii 6b, Rome 00185 and 3Department of Neuroscience, University of Rome ‘Tor Vergata’ Via Montpellier 1, 00133 Rome, Italy

*To whom correspondence should be addressed. Tel: +39 0672594376; Fax: +39 0672594326; Email: desideri{at}uniroma2.it

Received May 14, 2009. Accepted August 29, 2009.

The functional and structural-dynamical properties of the Lys681Ala mutation in the human topoisomerase IB linker domain have been investigated by catalytic assays and molecular dynamics simulation. The mutant is characterized by a comparable cleavage and a strongly reduced religation rate when compared to the wild type protein. The mutant also displays perturbed linker dynamics, as shown by analysis of the principal components of the motion, and a reduced electrostatic interaction with DNA. Inspection of the inter atomic distances in proximity of the active site shows that in the mutant the distance between the amino group of Lys532 side chain and the 5' OH of the scissile phosphate is longer than the wild type enzyme, providing an atomic explanation for the reduced religation rate of the mutant. Taken together these results indicate the existence of a long range communication between the linker domain and the active site region and points out the crucial role of the linker in the modulation of the catalytic activity.

The authors wish it to be known that, in their opinion, the first two 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.