Structure of the 1:1 netropsin–decamer d(CCIICICCII)₂ complex with a single bound netropsin

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 Å. The complex crystallizes in space group C2, with unit-cell parameters a = 62.40, b = 24.47, c = 36.31 Å, β = 110.09° 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 N1H₂ to the O₂ of cytosine 2 and through N10H₂ to N₃ 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.