1BP8

4:2:1 mithramycin:Mg++:d(ACCCGGGT)2 complex

Summary for 1BP8

• Entry DOI: 10.2210/pdb1bp8/pdb
• Descriptor: 5'-D(*AP*CP*CP*CP*GP*GP*GP*T)-3', beta-D-Olivopyranose-(1-3)-beta-D-Olivopyranose, 2,6-dideoxy-3-C-methyl-beta-D-ribo-hexopyranose-(1-3)-2,6-dideoxy-beta-D-galactopyranose-(1-3)-beta-D-Olivopyranose, ... (5 entities in total)
• Functional Keywords: mithramycin, dna, oligonucleotide
• Total number of polymer chains: 2
• Total formula weight: 9260.53

Authors

Keniry, M.A.,Owen, E.A.,Shafer, R.H. (deposition date: 1998-08-13, release date: 1999-08-16, Last modification date: 2023-12-27)

Primary citation

Keniry, M.A.,Owen, E.A.,Shafer, R.H.
The three-dimensional structure of the 4:1 mithramycin:d(ACCCGGGT)2 complex: evidence for an interaction between the E saccharides
Biopolymers, 54:104-114, 2000

PubMed Abstract: Mithramycin and chromomycin, two antitumor drugs, each having an identical aglycone and nearly identical disaccharide and trisaccharide side chains, have differing binding properties to a small oligonucleotide, d(ACCCGGGT)(2) (M. A. Keniry et al., Journal of Molecular Biology, 1993, Vol. 231, pp. 753-767). In order to understand the forces that induce four mithramycin molecules to bind to d(ACCCGGGT)(2) instead of two drug molecules in the case of chromomycin, the structure of the 4:2:1 mithramycin: Mg(2+):d(ACCCGGGT)(2) complex was investigated by (1)H-nmr and restrained molecular dynamics. The resulting three-dimensional model showed that in order to accommodate the close approach of one neighboring mithramycin dimer, the inwardly directed CDE saccharide chain of the neighboring mithramycin dimer undergoes a conformational change such that the E saccharide no longer spans the minor groove but reorients so that the hydrophilic face of the E saccharides from the two dimers oppose each other. Two hydrogen bonds are formed between the hydroxyl groups of the two opposing E saccharide groups. The results are interpreted in terms of the differences in stereochemistry and functional group substitutions between mithramycin and chromomycin. A mithramycin dimer is able to self-associate on an oligonucleotide template because it has two hydroxyl groups on the same face of its terminal E saccharide. A chromomycin dimer is unable to self-associate because one of these hydroxyl groups is acetylated and the neighboring hydroxyl group has a stereochemistry that cannot permit close contact of the hydroxyl group with a neighbouring chromomycin dimer.

PubMed: 10861371
DOI: 10.1002/1097-0282(200008)54:2<104::AID-BIP3>3.0.CO;2-2

Experimental method

SOLUTION NMR