Abstract

The crystal structure of the 1:1 complex of netropsin and the B-DNA decamer d(CCIICICCII)(2) has been elucidated and refined to an R factor of 19.6% and an R(free) of 24.7% using 1790 reflections in the resolution range 8-2.4 A. The complex crystallizes in space group C2, with unit-cell parameters a = 62.40, b = 24.47, c = 36.31 A, beta = 110.09 degrees and one molecule of netropsin in the asymmetric unit; the rest of the minor groove is filled with six water molecules. The structure was solved by the molecular-replacement method using the DNA model d(CCCCCIIIII)(2) from the 2:1 netropsin complex by removing both bound netropsins (Chen et al., 1998). Surprisingly, only one netropsin molecule is found to bind to the present decamer, covering residues 2-6 at the upper stream of the duplex. The positively charged guanidinium head is hydrogen bonded through N1H(2) to the O(2) of cytosine 2 and through N10H(2) to N(3) of inosine 6. The three amide N-H groups of the peptides face the minor groove and form three sets of bifurcated hydrogen bonds with the base atoms. The central part of the drug (C3-N8) is nearly conjugated. The preference of the cytosine carbonyl O2 atoms over the inosine N3 atoms in hydrogen bonding is seen. The drug-bound region has more uniform twists, roll angles, propeller twists and minor-groove widths compared with the water-bound region.