CRYSTAL STRUCTURE OF A l:l COMPLEX BETWEEN NETROPSIN AND D(CGCAATTGCG)₂. Christine M. Nunn, Neil Spink, ^*Elspeth Garman, Stephen Neidle, CRC, Biomolecular Structure Unit, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 SNG, UK, ^*Laboratory of Molecular Biophysics, University of Oxford, Oxford, OX1 3QU, UK

DNA minor groove binding drugs such as netropsin, distamycin and pentamidine have been extensively studied bound to DNA dodecamer sequences which contain a central AT-rich base-pair region. In this study the natuarally occuring antibiotic netropsin has been cocrystallised with the DNA decamer d(CGCAATTGCG)₂ and the structure determined to 2.4Å resolution. The netropsin molecule displays AT specificity with hydrogen bonding contacts from the amide NH groups of netropsin to adenine N3 and thymine O2 atoms lying along the floor of the groove.

The crystal structure of native d(CGCAATTGCG)₂ has been determined in two previous studies.^1,2 Within the netropsin: DNA complex the central eight bases of each single strand form Watson-Crick base-pairs and duplex of the type d(GCAATTGC)₂, whilst the terminal 5'-C and G-3' bases are unpaired. The two terminal guanosines of each single strand lie within the minor groove of a symmetry-related duplex with hydrogen-bonding interactions via guanine atoms N2 and N3 and atom O4' of the deoxyribose sugar to a C G base-pair. The terminal unpaired cytosine bases lie within the major groove of adjacent duplexes to form base triplets of the type C G C with hydrogen-bonding interactions to a C G base-pair.

1. N. Spink et al., Proc. Natl. Acad. Sci. USA (1995) 92 10767-10771.

2. See Poster by Wood, Nunn & Neidle.