CRYSTAL-STRUCTURE OF THE DNA DECAMER D(CGCAATTGCG) COMPLEXED WITH THEMINOR-GROOVE BINDING-DRUG NETROPSIN

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.