1da0
From Proteopedia
|
DNA-DRUG INTERACTIONS: THE CRYSTAL STRUCTURE OF D(CGATCG) COMPLEXED WITH DAUNOMYCIN
Overview
The structure of a d(CGATCG)-daunomycin complex has been determined by, single crystal X-ray diffraction techniques. Refinement, with the location, of 40 solvent molecules, using data up to 1.5 A, converged with a final, crystallographic residual, R = 0.25 (RW = 0.22). The tetragonal crystals, are in space group P4(1)2(1)2, with cell dimensions of a = 27.98 A and c =, 52.87 A. The self-complementary d(CGATCG) forms a distorted right-handed, helix with a daunomycin molecule intercalated at each d(CpG) step. The, daunomycin aglycon chromophore is oriented at right-angles to the long, axis of the DNA base-pairs. This head-on intercalation is stabilized by, direct hydrogen bonds and indirectly via solvent-mediated, hydrogen-bonding interactions between the chromophore and its, intercalation site base-pairs. The cyclohexene ring and amino sugar, substituent lie in the minor groove. The amino sugar N-3' forms a hydrogen, bond with O-2 of the next neighbouring thymine. This electrostatic, interaction helps position the sugar in a way that results in extensive, van der Waals contacts between the drug and the DNA. There is no, interaction between daunosamine and the DNA sugar-phosphate backbone. We, present full experimental details and all relevant conformational, parameters, and use the comparison with a d(CGTACG)-daunomycin complex to, rationalize some neighbouring sequence effects involved in daunomycin, binding.
About this Structure
1DA0 is a Protein complex structure of sequences from [1] with DM1 as ligand. Full crystallographic information is available from OCA.
Reference
DNA-drug interactions. The crystal structure of d(CGATCG) complexed with daunomycin., Moore MH, Hunter WN, d'Estaintot BL, Kennard O, J Mol Biol. 1989 Apr 20;206(4):693-705. PMID:2738914
Page seeded by OCA on Sun Nov 25 02:51:08 2007
