263D

ISOHELICITY AND PHASING IN DRUG-DNA SEQUENCE RECOGNITION: CRYSTAL STRUCTURE OF A TRIS(BENZIMIDAZOLE)-OLIGONUCLEOTIDE COMPLEX

Summary for 263D

• Entry DOI: 10.2210/pdb263d/pdb
• Descriptor: DNA (5'-D(*CP*GP*CP*AP*AP*AP*TP*TP*TP*GP*CP*G)-3'), 2''-(4-METHOXYPHENYL)-5-(3-AMINO-1-PYRROLIDINYL)-2,5',2',5''-TRI-BENZIMIDAZOLE (3 entities in total)
• Functional Keywords: b-dna, double helix, complexed with drug, dna
• Total number of polymer chains: 2
• Total formula weight: 7866.43

Authors

Clark, G.R.,Gray, E.J.,Neidle, S.,Li, Y.-H.,Leupin, W. (deposition date: 1996-09-27, release date: 1996-10-15, Last modification date: 2024-04-03)

Primary citation

Clark, G.R.,Gray, E.J.,Neidle, S.,Li, Y.H.,Leupin, W.
Isohelicity and phasing in drug--DNA sequence recognition: crystal structure of a tris(benzimidazole)--oligonucleotide complex.
Biochemistry, 35:13745-13752, 1996

PubMed Abstract: The crystal structure is reported of a tris(benzimidazole) analogue of the minor-groove drug Hoechst 33258 bound to the sequence d(CGCAAATTTGCG)2. The structure has been refined to an R factor of 17.4% at a resolution of 2.2 A. The ligand covers approximately 7 1/2 base pairs, including the 5'-AAATTT central sequence. This has an exceptionally narrow minor-groove width, together with high propeller twists for individual base pairs. The ligand has a highly twisted structure, with an overall twist of 50 degrees between aromatic rings. All three benzimidazole subunits are in register with the DNA, and there is a symmetric group of six hydrogen bonds between ligand and A.T base-pair edges. By contrast, the ligand does not show an optimal isohelical fit to the DNA. The correct phasing of drug and DNA base pairs is ensured by a number of changes to the DNA such that the central 5'-AAATTT region is slightly unwound relative to the structures of other noncovalent minor-groove drug complexes.

PubMed: 8901516
DOI: 10.1021/bi960421m

Experimental method

X-RAY DIFFRACTION (2.2 Å)