The crystal structure of netropsin bound to the decamer d(CGCAATTGCG) has been
determined at 2.4 A resolution. This is the first example of a crystal structure
of netropsin bound to decamer DNA. The central eight bases of each DNA
single-strand base pair with a self-complementary strand to form an octamer
B-DNA duplex. These duplexes lie end to end within the unit cell. The terminal
5'-C and G-3' bases are unpaired and interact with the neighboring duplexes via
interactions within both the major and minor groove to form base triplet
interactions of the type C(+)-G x C and G*(G x C), respectively. The triplet
interaction of the type C(+)-G x C is known to exist within triplex DNA with the
C+ base oriented parallel with the Watson-Crick guanine base to which it
hydrogen bonds. The netropsin molecule lies within the minor groove of the
octamer duplex and assumes a class I type position, with bifurcated
hydrogen-bonding interactions from the amide groups of the netropsin to the A x
T base pairs of the minor groove. The netropsin molecule fits within a five base
pair long minor groove site by bending of the flexible amidinium group at one
end of the drug.
