Molecular Structure of the Netropsin-d(CGCGATATCGCG) Complex: DNA Conformation in an Alternating AT Segment

Miquel Coll, Juan Aymami, Gijs A. van der Marel, Jacques H. van Boom, Alexander Rich, Andrew H.J. Wang

研究成果: 雜誌貢獻文章同行評審

215 引文 斯高帕斯(Scopus)

摘要

The molecular structure of the complex between a minor groove binding drug (netropsin) and the DNA dodecamer d(CGCGATATCGCG) has been solved and refined by single-crystal X-ray diffraction analysis to a final R factor of 20.0% to 2.4-Å resolution. The crystal is similar to that of the other related dodecamers with unit cell dimensions of a = 25.48 Å, b = 41.26 Å, and c = 66.88 Å in the space group P212121. In the complex, netropsin binds to the central ATAT tetranucleotide segment in the narrow minor groove of the dodecamer B-DNA double helix as expected. However, in the structural refinement the drug is found to fit the electron density in two orientations equally well, suggesting the disordered model. This agrees with the results from solution studies (chemical footprinting and NMR) of the interactions between minor groove binding drugs (e.g., netropsin and distamycin A) and DNA. The stabilizing forces between drug and DNA are provided by a combination of ionic, van der Waals, and hydrogen-bonding interactions. No bifurcated hydrogen bond is found between netropsin and DNA in this complex due to the unique dispositions of the hydrogen-bond acceptors (N3 of adenine and O2 of thymine) on the floor of the DNA minor groove. Two of the four AT base pairs in the ATAT stretch have low propeller twist angles, even though the DNA has a narrow minor groove. Alternating helical twist angles are observed in the ATAT stretch with lower twist in the ApT steps than in the TpA step.

原文英語
頁(從 - 到)310-320
頁數11
期刊Biochemistry
28
發行號1
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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