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| {{STRUCTURE_1bp8| PDB=1bp8 | SCENE= }} | | {{STRUCTURE_1bp8| PDB=1bp8 | SCENE= }} |
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- | '''4:2:1 MITHRAMYCIN:MG2+:D(ACCCGGGT)2 COMPLEX'''
| + | ===4:2:1 MITHRAMYCIN:MG2+:D(ACCCGGGT)2 COMPLEX=== |
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- | ==Overview==
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- | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10861371}}, adds the Publication Abstract to the page |
| + | (as it appears on PubMed at http://www.pubmed.gov), where 10861371 is the PubMed ID number. |
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| + | {{ABSTRACT_PUBMED_10861371}} |
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| ==About this Structure== | | ==About this Structure== |
- | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BP8 OCA]. | + | Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BP8 OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Nmr]] | | [[Category: Nmr]] |
| [[Category: Oligonucleotide]] | | [[Category: Oligonucleotide]] |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:47:45 2008'' | + | |
| + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 19:29:30 2008'' |
Revision as of 16:29, 30 June 2008
Template:STRUCTURE 1bp8
4:2:1 MITHRAMYCIN:MG2+:D(ACCCGGGT)2 COMPLEX
Template:ABSTRACT PUBMED 10861371
About this Structure
Full experimental information is available from OCA.
Reference
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 Mon Jun 30 19:29:30 2008