1bp8
4:2:1 MITHRAMYCIN:MG2+:D(ACCCGGGT)2 COMPLEX
|
OverviewOverview
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.Copyright 2000 John Wiley & Sons, Inc.
About this StructureAbout this Structure
1BP8 is a Protein complex structure of sequences from [1] with MG, MDA and DXB as ligands. Full crystallographic information is available from OCA.
ReferenceReference
The three-dimensional structure of the 4:1 mithramycin:d(ACCCGGGT)(2) complex: evidence for an interaction between the E saccharides., Keniry MA, Owen EA, Shafer RH, Biopolymers. 2000 Aug;54(2):104-14. PMID:10861371
Page seeded by OCA on Sun Nov 25 00:26:58 2007