HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 23, 24552-24560, June 4, 2004

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 279/23/24552    most recent M311751200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gómez-Pinto, I. Articles by González, C. Search for Related Content PubMed PubMed Citation Articles by Gómez-Pinto, I. Articles by González, C. Social Bookmarking                      What's this?

Effect of Bulky Lesions on DNA

SOLUTION STRUCTURE OF A DNA DUPLEX CONTAINING A CHOLESTEROL ADDUCT^*

Irene Gómez-Pinto, Elena Cubero, Susana G. Kalko, Vania Monaco¶, Gijs van der Marel¶, Jacques H. van Boom¶, Modesto Orozco||, and Carlos González**

From the Instituto de Química Física "Rocasolano," Consejo Superior de Investigaciones Científicas, C/. Serrano 119, 28006 Madrid, Spain, ^¶Gorlaeus Laboratories, Leiden University, 2300 RA Leiden, The Netherlands, and Department de Bioquímica, Universitat de Barcelona, C/. Martí i Franquès 1-11, 08028 Barcelona, Spain and Institut de Recerca Biomèdica, Parc Científic de Barcelona, Josep Samitier 1-5 Barcelona 08028, Spain

The three-dimensional solution structure of two DNA decamers of sequence d(CCACXGGAAC)-(GTTCCGGTGG) with a modified nucleotide containing a cholesterol derivative (X) in its C1 '(chol) or C1 '(chol) diastereoisomer form has been determined by using NMR and restrained molecular dynamics. This DNA derivative is recognized with high efficiency by the UvrB protein, which is part of the bacterial nucleotide excision repair, and the anomer is repaired more efficiently than the one. The structures of the two decamers have been determined from accurate distance constraints obtained from a complete relaxation matrix analysis of the NOE intensities and torsion angle constraints derived from J-coupling constants. The structures have been refined with molecular dynamics methods, including explicit solvent and applying the particle mesh Ewald method to properly evaluate the long range electrostatic interactions. These calculations converge to well defined structures whose conformation is intermediate between the A- and B-DNA families as judged by the root mean square deviation but with sugar puckerings and groove shapes corresponding to a distorted B-conformation. Both duplex adducts exhibit intercalation of the cholesterol group from the major groove of the helix and displacement of the guanine base opposite the modified nucleotide. Based on these structures and molecular dynamics calculations, we propose a tentative model for the recognition of damaged DNA substrates by the UvrB protein.

Received for publication, October 27, 2003 , and in revised form, March 29, 2004.

The atomic coordinates and structure factors (codes 1SP6 and 1SSJ) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by the Spanish Ministry of Science and Technology Grants BQU2001-3693-C02-02, PM99-0046, and European Union project QLG1-CT-1999-00008. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains tables with the assignment lists, average values and order parameters of the dihedral torsion angles, and J-coupling constant information, two figures showing the distribution of distance constraints, and some representative helix parameters..

^|| To whom correspondence may be addressed. E-mail: modesto{at}mmb.pcb.ub.es.

^** To whom correspondence may be addressed. Fax: 34-934037157; E-mail: cgonzalez{at}iqfr.csic.es.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Perez, F. Lankas, F. J. Luque, and M. Orozco Towards a molecular dynamics consensus view of B-DNA flexibility Nucleic Acids Res., April 1, 2008; 36(7): 2379 - 2394. [Abstract] [Full Text] [PDF]

				J. P. Lopez-Alonso, M. Bruix, J. Font, M. Ribo, M. Vilanova, M. Rico, G. Gotte, M. Libonati, C. Gonzalez, and D. V. Laurents Formation, Structure, and Dissociation of the Ribonuclease S Three-dimensional Domain-swapped Dimer. J. Biol. Chem., April 7, 2006; 281(14): 9400 - 9406. [Abstract] [Full Text] [PDF]