A CONTINUOUS TRANSITION FROM A-DNA TO B-DNA IN THE 1 1-COMPLEX BETWEEN NOGALAMYCIN AND THE HEXAMER-DCCCGGG/

The antibiotic nogalamycin, a drug with high specificity for TG and CG steps in double-stranded DNA, has been crystallized as a 1:1 complex with the hexamer d(CCCGGG). The antibiotic is inserted at the central CG step of the duplex, with the two sugars oriented in the same direct ion and with strong interactions with the DNA within the grooves, The amino-glucose residue makes an integral part of a well defined major g roove hydration network with van der Waals contacts and several strong hydrogen bonds to the duplex, The nogalose residue resides in the min or groove, making primarily van der Waals contacts, The single site al lows an accurate molecular description of the intercalation, without p erturbations from end effects observed previously, The local unwinding induced by nogalamycin is completely relaxed 2 base pairs away from t he intercalation site. The two strands of the DNA show a continuous de formation from the A to the B form: 1) the cytosines toward the 5' end of the nogalomycin site in each strand have c3'-endo conformations wh ile 5 guanosines toward the 3' ends have c2'-endo conformations; 2) wi thin each strand, the phosphate-phosphate distances increase in a cont inuous manner from 5.7 Angstrom (A-form) to 7.1 Angstrom (B-form).