1JHI

Solution Structure of a Hedamycin-DNA complex

Summary for 1JHI

• Entry DOI: 10.2210/pdb1jhi/pdb
• Descriptor: 5'-D(*AP*CP*CP*(HEH)GP*GP*T)-3', HEDAMYCIN (2 entities in total)
• Functional Keywords: duplex dna, hedamycin, dna
• Total number of polymer chains: 2
• Total formula weight: 4367.29

Authors

Owen, E.A.,Burley, G.A.,Carver, J.A.,Wickham, G.,Keniry, M.A. (deposition date: 2001-06-27, release date: 2003-07-08, Last modification date: 2024-05-22)

Primary citation

Owen, E.A.,Burley, G.A.,Carver, J.A.,Wickham, G.,Keniry, M.A.
Structural investigation of the hedamycin:d(ACCGGT)2 complex by NMR and restrained molecular dynamics.
Biochem.Biophys.Res.Commun., 290:1602-1608, 2002

PubMed Abstract: 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.

PubMed: 11820806
DOI: 10.1006/bbrc.2002.6369

Experimental method

SOLUTION NMR