SEQUENCE-DEPENDENT EFFECTS IN DRUG-DNA INTERACTION - THE CRYSTAL-STRUCTURE OF HOECHST-33258 BOUND TO THE D(CGCAAATTTGCG)(2) DUPLEX

被引:118
作者
SPINK, N [1 ]
BROWN, DG [1 ]
SKELLY, JV [1 ]
NEIDLE, S [1 ]
机构
[1] INST CANC RES,CRC,BIOMOLEC STRUCT UNIT,SUTTON SM2 5NG,SURREY,ENGLAND
关键词
D O I
10.1093/nar/22.9.1607
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
The bis-benzimidazole drug Hoechst 33258 has been co-crystallized with the dodecanucleotide sequence d(CGCAAATTTGCG)(2). The structure has been solved by molecular replacement and refined to an R factor of 18.5% for 2125 reflections collected on a Xentronics area detector. The drug is bound in the minor groove, at the five base-pair site 5'-ATTTG and is in a unique orientation. This is displaced by one base pair in the 5' direction compared to previously-determined structures of this drug with the sequence d(CGCGAATTCGCG)(2). Reasons for this difference in behaviour are discussed in terms of several sequence-dependent structural features of the DNA, with particular reference to differences in propeller twist and minor-groove width.
引用
收藏
页码:1607 / 1612
页数:6
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