Structural basis of DNA quadruplex recognition by an acridine drug.
The crystal structure of a complex between the bimolecular human telomeric quadruplex d(TAGGGTTAGGGT)2 and the experimental anticancer drug BRACO-19, has been determined, to 2.5 A resolution. The binding site for the BRACO-19 molecule is at the interface of two parallel-folded quadruplexes, sandwiched between a G-tetrad surface and a TATA tetrad, and held in the site by networks of water molecules. The structure rationalizes the existing structure-activity data and provides a starting-point for the structure-based design of quadruplex-binding ligands
Campbell
Nancy H
NH
Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Parkinson
Gary N
GN
Reszka
Anthony P
AP
Neidle
Stephen
S
D000166:Acridines / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D016385:TATA Box; D016615:Telomere / Q000737:chemistry
D000166:Acridines; D004247:DNA; C454064:BRACO-19