1eg6

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spinqualitylabelsall models 1eg6, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE ANALYSIS OF D(CG(5-BRU)ACG) COMPLEXES TO A PHENAZINE

Overview

The structure of the duplex d[CG(5-BrU)ACG](2) bound to, 9-bromophenazine-4-carboxamide has been solved through MAD phasing at 2.0, A resolution. It shows an unexpected and previously unreported, intercalation cavity stabilized by the drug and novel binding modes of, Co(2+) ions at certain guanine N7 sites. For the intercalation cavity the, terminal cytosine is rotated to pair with the guanine of a, symmetry-related duplex to create a pseudo-Holliday junction geometry, with two such cavities linked through the minor groove interactions of the, N2/N3 guanine sites at an angle of 40 degrees, creating a quadruplex-like, structure. The mode of binding of the drug is shown to be disordered, with, the major conformations showing the side chain bound to the N7 position of, adjacent guanines. The other end of the duplex exhibits a terminal base, fraying in the presence of Co(2+) ions linking symmetry-related guanines, causing the helices to intertwine through the minor groove. The, stabilization of the structure by the intercalating drug shows that this, class of compound may bind to DNA junctions as well as duplex DNA or to, strand-nicked DNA ('hemi-intercalated'), as in the cleavable complex. This, suggests a structural basis for the dual poisoning of topoisomerase I and, II enzymes by this family of drugs.

About this Structure

1EG6 is a Protein complex structure of sequences from [1] with 3CO, BR and BFA as ligands. Full crystallographic information is available from OCA.

Reference

Guanine specific binding at a DNA junction formed by d[CG(5-BrU)ACG](2) with a topoisomerase poison in the presence of Co(2+) ions., Thorpe JH, Hobbs JR, Todd AK, Denny WA, Charlton P, Cardin CJ, Biochemistry. 2000 Dec 12;39(49):15055-61. PMID:11106483

Page seeded by OCA on Sat Nov 24 22:12:10 2007