Three-dimensional crystal structure of the A-tract DNA dodecamer d(CGCAAATTTGCG) complexed with the minor-groove-binding drug Hoechst 33258.
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.
Vega
M C
MC
Departament de Biologia Molecular i Cel-lular, Centre d'Investigació i Desenvolupament-C.S.I.C., Barcelona, Spain.
García Sáez
I
I
Aymamí
J
J
Eritja
R
R
Van der Marel
G A
GA
Van Boom
J H
JH
Rich
A
A
Coll
M
M
D001483:Base Sequence; D001665:Binding Sites; D006690:Bisbenzimidazole / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D007091:Image Processing, Computer-Assisted; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D004247:DNA; D006690:Bisbenzimidazole