1DA0

DNA-DRUG INTERACTIONS: THE CRYSTAL STRUCTURE OF D(CGATCG) COMPLEXED WITH DAUNOMYCIN

Summary for 1DA0

• Entry DOI: 10.2210/pdb1da0/pdb
• Descriptor: DNA (5'-D(*CP*GP*AP*TP*CP*G)-3'), DAUNOMYCIN (2 entities in total)
• Functional Keywords: right handed dna, double helix, complexed with drug, dna
• Total number of polymer chains: 1
• Total formula weight: 2336.74

Authors

Moore, M.H.,Hunter, W.N.,Langlois D'Estaintot, B.,Kennard, O. (deposition date: 1992-10-17, release date: 1993-07-15, Last modification date: 2024-02-07)

Primary citation

Moore, M.H.,Hunter, W.N.,d'Estaintot, B.L.,Kennard, O.
DNA-drug interactions. The crystal structure of d(CGATCG) complexed with daunomycin.
J.Mol.Biol., 206:693-705, 1989

PubMed Abstract: 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.

PubMed: 2738914
DOI: 10.1016/0022-2836(89)90577-9

Experimental method

X-RAY DIFFRACTION (1.5 Å)