3FSI

Crystal structure of a trypanocidal 4,4'-Bis(imidazolinylamino)diphenylamine bound to DNA

3FSI の概要

• エントリーDOI: 10.2210/pdb3fsi/pdb
• 分子名称: Reverse transcriptase domain, 5'-D(*CP*TP*TP*AP*AP*TP*TP*C)-3', 5'-D(P*GP*AP*AP*TP*TP*AP*AP*G)-3', ... (6 entities in total)
• 機能のキーワード: transferase/dna mmlv rt, protein-dna complex, drug-dna complex, cd27, antitrypanosomal, dna integration, dna recombination, nucleotidyltransferase, transferase, transferase-dna complex, transferase/dna
• 由来する生物種: Moloney murine leukemia virus (Virus)
• 細胞内の位置: Gag-Pol polyprotein: Host cell membrane ; Lipid-anchor . Matrix protein p15: Virion . Capsid protein p30: Virion . Nucleocapsid protein p10: Virion : P03355
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 34416.17

構造登録者

Glass, L.S.,Georgiadis, M.M.,Goodwin, K.D. (登録日: 2009-01-09, 公開日: 2009-05-19, 最終更新日: 2023-09-06)

主引用文献

Glass, L.S.,Nguyen, B.,Goodwin, K.D.,Dardonville, C.,Wilson, W.D.,Long, E.C.,Georgiadis, M.M.
Crystal structure of a trypanocidal 4,4'-bis(imidazolinylamino)diphenylamine bound to DNA.
Biochemistry, 48:5943-5952, 2009

PubMed Abstract: The pursuit of small molecules that bind to DNA has led to the discovery of selective and potent antitrypanosomal agents, specifically 4,4'-bis(imidazolinylamino)- and 4,4'-bis(guanidino)diphenylamine compounds, CD27 and CD25, respectively. Although the antitrypanosomal properties of these compounds have been characterized, further development of this series of compounds requires assessment of their DNA site selectivities and affinities. Toward this end, both compounds have been analyzed and found to selectively bind AT sequences. However, CD27 was found to bind with higher affinity to 5'-AATT than 5'-ATAT while CD25 bound more weakly but equally well to either sequence. To detail the nature of its interactions with DNA, the crystal structure of CD27, bound to its preferred DNA-binding site 5'-AATT within a self-complementary oligonucleotide, 5'-d(CTTAATTCGAATTAAG), was determined at 1.75 A using a host-guest approach. Although CD27 is predicted to be highly twisted in its energy-minimized state, it adopts a more planar crescent shape when bound in the minor groove of the DNA. Interactions of CD27 with 5'-AATT include bifurcated hydrogen bonds, providing a basis for selectivity of this site, and favorable van der Waals interactions in a slightly widened minor groove. Thus, an induced fit results from conformational changes in both the ligand and the DNA. Our studies suggest a basis for understanding the mechanism of the antitrypanosomal activity of these symmetric diphenylamine compounds.

PubMed: 19405506
DOI: 10.1021/bi900204w

実験手法

X-RAY DIFFRACTION (1.75 Å)