3-DIMENSIONAL CRYSTAL-STRUCTURE OF THE A-TRACT DNA DODECAMER D(CGCAAATTTGCG) COMPLEXED WITH THE MINOR-GROOVE-BINDING DRUG HOECHST-33258

被引:121
作者
VEGA, MC
SAEZ, IG
AYMAMI, J
ERITJA, R
VANDERMAREL, GA
VANBOOM, JH
RICH, A
COLL, M
机构
[1] CSIC, CTR INVEST & DESENVOLUPAMENT, DEPT BIOL MOLEC & CELLULAR, E-08034 BARCELONA, SPAIN
[2] UNIV POLITECN CATALUNYA, DEPT ENGN QUIM, BARCELONA, SPAIN
[3] LEIDEN STATE UNIV, GORLAEUS LABS, 2300 RA LEIDEN, NETHERLANDS
[4] MIT, DEPT BIOL, CAMBRIDGE, MA USA
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1994年 / 222卷 / 03期
关键词
D O I
10.1111/j.1432-1033.1994.tb18917.x
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 molecular structure of the DNA A-tract dodecamer d(CGCAAATTTGCG) complexed with the drug Hoechst 33258 has been determined by X-ray diffraction analysis. The Hoechst molecule binds in the DNA minor groove covering the sequence AATTT of the central A-tract, with the piperazine group close to one of the GC regions. The drug molecule makes two three-centered hydrogen bonds from the nitrogen atoms of the benzimidazole rings to the N3 and O2 atoms of the DNA bases. Although a high propeller twist is observed in the A-tract, only one unsymmetrical three-centered hydrogen bond is present in the DNA major groove. The structure is compared with other minor-groove-binding drug complexes and the influence of these drugs on DNA A-tracts is discussed.
引用
收藏
页码:721 / 726
页数:6
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