102D

SEQUENCE-DEPENDENT DRUG BINDING TO THE MINOR GROOVE OF DNA: THE CRYSTAL STRUCTURE OF THE DNA DODECAMER D(CGCAAATTTGCG)2 COMPLEXED WITH PROPAMIDINE

Summary for 102D

• Entry DOI: 10.2210/pdb102d/pdb
• Descriptor: DNA (5'-D(*CP*GP*CP*AP*AP*AP*TP*TP*TP*GP*CP*G)-3'), 1,3-BIS(AMIDINOPHENOXY)PROPANE (3 entities in total)
• Functional Keywords: b-dna, double helix, complexed with drug, dna
• Total number of polymer chains: 2
• Total formula weight: 7637.17

Authors

Nunn, C.M.,Neidle, S. (deposition date: 1994-12-15, release date: 1995-02-07, Last modification date: 2024-02-07)

Primary citation

Nunn, C.M.,Neidle, S.
Sequence-dependent drug binding to the minor groove of DNA: crystal structure of the DNA dodecamer d(CGCAAATTTGCG)2 complexed with propamidine.
J.Med.Chem., 38:2317-2325, 1995

PubMed Abstract: The DNA-binding ligand propamidine, an analogue of the drug pentamidine which is used in the treatment of acquired immune deficiency syndrome (AIDS)-associated Pneumocystis carinii, has been cocrystallized with the DNA sequence d(CGCAAATTTGCG)2, and the crystal structure of the complex has been determined using data from 8 to 2.2 A resolution. The R factor converged to 15.5% with the inclusion of 73 water molecules. The structure shows binding of the propamidine molecule within the AT tract of the DNA minor groove with a shift from the center of the duplex toward the 3' end of ca. 2 A. The long AT tract of six base pairs in length allows the propamidine many potential binding sites in the DNA groove, and its binding is seen to occur where there is least perturbation to the DNA from that seen in the native structure. The interactions with bases are distinct from those previously observed for the sequence d(CGCGAATTCGCG)2.

PubMed: 7608897
DOI: 10.1021/jm00013a008

Experimental method

X-RAY DIFFRACTION (2.2 Å)