4OCD

In and Out the minor groove: Interaction of an AT rich-DNA with the CD27 drug

4OCD の概要

• エントリーDOI: 10.2210/pdb4ocd/pdb
• 分子名称: d(AAAATTTT), N1-(4,5-dihydro-1H-imidazol-2-yl)-N4-(4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzene-1,4-diamine (3 entities in total)
• 機能のキーワード: dna minor groove binding drugs, all-at dna, dicationic drug, imidazoline drug, dna
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 8280.14

構造登録者

Acosta-Reyes, F.J.,Dardonville, C.,de Koning, H.P.,Natto, M.,Subirana, J.A.,Campos, J.L. (登録日: 2014-01-08, 公開日: 2014-06-11, 最終更新日: 2024-02-28)

主引用文献

Acosta-Reyes, F.J.,Dardonville, C.,de Koning, H.P.,Natto, M.,Subirana, J.A.,Campos, J.L.
In and out of the minor groove: interaction of an AT-rich DNA with the drug CD27
Acta Crystallogr.,Sect.D, D70:1614-1621, 2014

PubMed Abstract: The DNA of several pathogens is very rich in AT base pairs. Typical examples include the malaria parasite Plasmodium falciparum and the causative agents of trichomoniasis and trypanosomiases. This fact has prompted studies of drugs which interact with the minor groove of DNA, some of which are used in medical practice. Previous studies have been performed almost exclusively with the AATT sequence. New features should be uncovered through the study of different DNA sequences. In this paper, the crystal structure of the complex of the DNA duplex d(AAAATTTT)2 with the dicationic drug 4,4'-bis(imidazolinylamino)diphenylamine (CD27) is presented. The drug binds to the minor groove of DNA as expected, but it shows two new features that have not previously been described: (i) the drugs protrude from the DNA and interact with neighbouring molecules, so that they may act as cross-linking agents, and (ii) the drugs completely cover the whole minor groove of DNA and displace bound water. Thus, they may prevent the access to DNA of proteins such as AT-hook proteins. These features are also expected for other minor-groove binding drugs when associated with all-AT DNA. These findings allow a better understanding of this family of compounds and will help in the development of new, more effective drugs. New data on the biological interaction of CD27 with the causative agent of trichomoniasis, Trichomonas vaginalis, are also reported.

PubMed: 24914972
DOI: 10.1107/S139900471400697X

実験手法

X-RAY DIFFRACTION (2.1 Å)