VARIABILITY IN DNA MINOR-GROOVE WIDTH RECOGNIZED BY LIGAND-BINDING - THE CRYSTAL-STRUCTURE OF A BIS-BENZIMIDAZOLE COMPOUND BOUND TO THE DNA DUPLEX D(CGCGAATTCGCG)(2)

被引:43
作者
WOOD, AA
NUNN, CM
CZARNY, A
BOYKIN, DW
NEIDLE, S
机构
[1] INST CANC RES, CRC, BIOMOLEC STRUCT UNIT, SUTTON SM2 5NG, SURREY, ENGLAND
[2] GEORGIA STATE UNIV, DEPT CHEM, ATLANTA, GA 30303 USA
[3] GEORGIA STATE UNIV, CTR BIOTECHNOL & DRUG DESIGN, ATLANTA, GA 30303 USA
关键词
D O I
10.1093/nar/23.18.3678
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
An analogue of the DNA-binding compound Hoechst 33258, in which the piperazine ring has been replaced by an imidazoline group, has been cocrystallized with the dodecanucleotide sequence d(CGCGAATTCGCG)(2). The structure has been solved by X-ray diffraction analysis and has been refined to an R-factor of 19.7% at a resolution of 2.0 Angstrom. The ligand is found to bind in the minor groove, at the central four AATT base pairs of the B-DNA double helix, with the involvement of a number of van der Waals contacts and hydrogen bonds, There are significant differences in minor groove width for the two compounds, along much of the AATT region. In particular this structure shows a narrower groove at the 3' end of the binding site consistent with the narrower cross-section of the imidazole group compared with the piperazine ring of Hoechst 33258 and therefore a smaller perturbation in groove width, The higher binding affinity to DNA shown by this analogue compared with Hoechst 33258 itself, has been rationalised in terms of these have established that these molecules bind in the minor groove of differences.
引用
收藏
页码:3678 / 3684
页数:7
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