Binding of a Hoechst Dye to d(CGCGATATCGCG) and Its Influence on the Conformation of the DNA Fragment

Maria A.A.F.de C.T. Carrondo, Miquel Coll, Joan Aymami, Andrew H.J. Wang, Gijs A. van der Marel, Jacques H. van Boom, Alexander Rich

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169 引文 斯高帕斯(Scopus)

摘要

Hoechst dye 33258 is a planar drug molecule that binds to the minor groove of DNA, especially where there are a number of A·T base pairs. We have solved the structure of the Hoechst dye bound to the DNA dodecamer d(CGCGATATCGCG) at 2.3 Å. This structure is compared to that of the same dodecamer with the minor-groove-binding drug netropsin bound to it, as well as to structures that have been solved for this Hoechst dye bound to a DNA dodecamer containing the central four base pairs with the sequence AATT. We find that the position of the Hoechst drug in this dodecamer is quite different from that found in the other dodecamer since it has an opposite orientation compared to the other two structures. The drug covers three of the four A·T base pairs and extends its piperazine ring to the first G·C base pair adjacent to the alternating AT segment. Furthermore, the drug binding has modified the structure of the DNA dodecamer. Other DNA dodecamers with alternating AT sequences show an alternation in the size of the helical twist between the ApT step (small twist) and the TpA step (large twist). In this structure the alternation is reversed with larger twists in the ApT steps than in the TpA step. In addition, there is a rotation of one of the thymine bases in the DNA dodecamer that is associated with hydrogen bonding to the Hoechst drug. This structure illustrates the considerable plasticity found in the DNA molecule when it binds to different planar molecules inserted into the minor groove.

原文英語
頁(從 - 到)7849-7859
頁數11
期刊Biochemistry
28
發行號19
DOIs
出版狀態已發佈 - 1989
對外發佈

ASJC Scopus subject areas

  • 生物化學

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