Cm. Nunn et al., CRYSTAL-STRUCTURE OF THE DNA DECAMER D(CGCAATTGCG) COMPLEXED WITH THEMINOR-GROOVE BINDING-DRUG NETROPSIN, Biochemistry, 36(16), 1997, pp. 4792-4799
The crystal structure of netropsin bound to the decamer d(CGCAATTGCG)
has been determined at 2.4 Angstrom resolution. This is the first exam
ple of a crystal structure of netropsin bound to decamer DNA. The cent
ral eight bases of each DNA single-strand base pair with a self-comple
mentary 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 unp
aired and interact with the neighboring duplexes via interactions with
in both the major and minor groove to form base triplet interactions o
f the type C+-G . C and G(G . C), respectively. The triplet interacti
on of the type C+-G . C is known to exist within tripler 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 bifur
cated hydrogen-bonding interactions from the amide groups of the netro
psin to the A . T base pairs of the minor groove. The netropsin molecu
le fits within a five base pair long minor groove site by bending of t
he flexible amidinium group at one end of the drug.