1jhi

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Solution Structure of a Hedamycin-DNA complex

Overview

Hedamycin, a member of the pluramycin family of drugs, displays a range of, biological responses including antitumor and antimicrobial activity. The, mechanism of action is via direct interaction with DNA through, intercalation between the bases of the oligonucleotide and alkylation of a, guanine residue at 5'-PyG-3' sites. There appears to be some minor, structural differences between two earlier studies on the interaction of, hedamycin with 5'-PyG-3' sites. In this study, a high-resolution NMR, analysis of the hedamycin:d(ACCGGT)2 complex was undertaken in order to, investigate the effect of replacing the thymine with a guanine at the, preferred 5'-CGT-3' site. The resultant structure was compared with, earlier work, with particular emphasis placed on the drug conformation., The structure of the hedamycin:d(ACCGGT)2 complex has many features in, common with the two previous NMR structures of hedamycin:DNA complexes but, differed in the conformation and orientation of the, N,N-dimethylvancosamine saccharide of hedamycin in one of these, structures. The preferential binding of hedamycin to 5'-CG-3' over, 5'-TG-3' binding sites is explained in terms of the orientation and, location of the N,N-dimethylvancosamine saccharide in the minor groove.

About this Structure

1JHI is a Protein complex structure of sequences from [1] with HEH as ligand. Full crystallographic information is available from OCA.

Reference

Structural investigation of the hedamycin:d(ACCGGT)2 complex by NMR and restrained molecular dynamics., Owen EA, Burley GA, Carver JA, Wickham G, Keniry MA, Biochem Biophys Res Commun. 2002 Feb 8;290(5):1602-8. PMID:11820806

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