2gb9
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(New page: 200px<br /><applet load="2gb9" size="350" color="white" frame="true" align="right" spinBox="true" caption="2gb9, resolution 1.70Å" /> '''d(CGTACG)2 crosslink...)
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Revision as of 13:23, 23 January 2008
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d(CGTACG)2 crosslinked bis-acridine complex
Overview
Acridine-4-carboxamides form a class of known DNA mono-intercalating, agents that exhibit cytotoxic activity against tumour cell lines due to, their ability to inhibit topoisomerases. Previous studies of bis-acridine, derivatives have yielded equivocal results regarding the minimum length of, linker necessary between the two acridine chromophores to allow, bis-intercalation of duplex DNA. We report here the 1.7 A resolution X-ray, crystal structure of a six-carbon-linked bis(acridine-4-carboxamide), ligand bound to d(CGTACG)2 molecules by non-covalent duplex cross-linking., The asymmetric unit consists of one DNA duplex containing an intercalated, acridine-4-carboxamide chromophore at each of the two CG steps. The other, half of each ligand is bound to another DNA molecule in a symmetry-related, manner, with the alkyl linker threading through the minor grooves. The two, crystallographically independent ligand molecules adopt distinct side, chain interactions, forming hydrogen bonds to either O6 or N7 on the major, groove face of guanine, in contrast to the semi-disordered state of, mono-intercalators bound to the same DNA molecule. The complex described, here provides the first structural evidence for the non-covalent, cross-linking of DNA by a small molecule ligand and suggests a possible, explanation for the inconsistent behaviour of six-carbon linked, bis-acridines in previous assays of DNA bis-intercalation.
About this Structure
2GB9 is a Protein complex structure of sequences from [1] with and as ligands. Full crystallographic information is available from OCA.
Reference
X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)2 molecules by a bis(9-aminoacridine-4-carboxamide) derivative., Hopcroft NH, Brogden AL, Searcey M, Cardin CJ, Nucleic Acids Res. 2006;34(22):6663-72. Epub 2006 Dec 1. PMID:17145714
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