1sp6
From Proteopedia
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A DNA duplex containing a cholesterol adduct (alpha-anomer)
Overview
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)alpha or C1 '(chol)beta, 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 alpha anomer is repaired more efficiently than the beta, 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.
About this Structure
1SP6 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Effect of bulky lesions on DNA: solution structure of a DNA duplex containing a cholesterol adduct., Gomez-Pinto I, Cubero E, Kalko SG, Monaco V, van der Marel G, van Boom JH, Orozco M, Gonzalez C, J Biol Chem. 2004 Jun 4;279(23):24552-60. Epub 2004 Mar 31. PMID:15047709
Page seeded by OCA on Sun Nov 25 00:56:18 2007
