1D58

THE MOLECULAR STRUCTURE OF A 4'-EPIADRIAMYCIN COMPLEX WITH D(TGATCA) AT 1.7 ANGSTROM RESOLUTION-COMPARISON WITH THE STRUCTURE OF 4'-EPIADRIAMYCIN D(TGTACA) AND D(CGATCG) COMPLEXES

Summary for 1D58

• Entry DOI: 10.2210/pdb1d58/pdb
• Descriptor: DNA (5'-D(*TP*GP*AP*TP*CP*A)-3'), 4'-EPIDOXORUBICIN (3 entities in total)
• Functional Keywords: right handed dna, double helix, complexed with drug, dna
• Total number of polymer chains: 1
• Total formula weight: 2352.76

Authors

Langlois D'Estaintot, B.,Gallois, B.,Brown, T.,Hunter, W.N. (deposition date: 1992-02-20, release date: 1992-10-15, Last modification date: 2024-02-07)

Primary citation

Langlois d'Estaintot, B.,Gallois, B.,Brown, T.,Hunter, W.N.
The molecular structure of a 4'-epiadriamycin complex with d(TGATCA) at 1.7A resolution: comparison with the structure of 4'-epiadriamycin d(TGTACA) and d(CGATCG) complexes.
Nucleic Acids Res., 20:3561-3566, 1992

PubMed Abstract: The structure of the complex between d(TGATCA) and the anthracycline 4'-epiadriamycin has been determined by crystallographic methods. The crystals are tetragonal, space group P4(1)2(1)2 with unit cell dimensions of a = 28.01, c = 52.95A. The asymmetric unit consists of one strand of hexanucleotide, one molecule of 4'-epiadriamycin and 34 waters. The R-factor is 20.2% for 1694 reflections with F greater than or equal to 2 sigma F to 1.7A. Two asymmetric units associate to generate a duplex complexed with two drug molecules at the d(TpG) steps of the duplex. The chromophore intercalates between these base pairs with the anthracycline amino-sugar positioned in the minor groove. The double helix is a distorted B-DNA type structure. Our structure determination of d(TGATCA) complexed to 4'-epiadriamycin allows for comparison with the previously reported structures of 4'-epiadriamycin bound to d(TGTACA) and to d(CGATCG). The three complexes are similar in gross features and the intercalation geometry is the same irrespective of whether a d(CpG) or d(TpG) sequence is involved. However, the orientation of the amino-sugar displays a dependence on the sequence adjacent to the intercalation site. The flexibility of this amino-sugar may help explain why this class of antibiotics displays a relative insensitivity to base sequence when they bind to DNA.

PubMed: 1641324
DOI: 10.1093/nar/20.14.3561

Experimental method

X-RAY DIFFRACTION (1.7 Å)