1bp8
From Proteopedia
(New page: 200px<br /><applet load="1bp8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bp8" /> '''4:2:1 MITHRAMYCIN:MG2+:D(ACCCGGGT)2 COMPLEX'...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1bp8.gif|left|200px]]<br /><applet load="1bp8" size=" | + | [[Image:1bp8.gif|left|200px]]<br /><applet load="1bp8" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1bp8" /> | caption="1bp8" /> | ||
'''4:2:1 MITHRAMYCIN:MG2+:D(ACCCGGGT)2 COMPLEX'''<br /> | '''4:2:1 MITHRAMYCIN:MG2+:D(ACCCGGGT)2 COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mithramycin and chromomycin, two antitumor drugs, each having an identical | + | 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 Structure== | ==About this Structure== | ||
| - | 1BP8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with MG, MDA and DXB as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1BP8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=MDA:'>MDA</scene> and <scene name='pdbligand=DXB:'>DXB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BP8 OCA]. |
==Reference== | ==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10861371 10861371] | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10861371 10861371] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Keniry, M | + | [[Category: Keniry, M A.]] |
| - | [[Category: Owen, E | + | [[Category: Owen, E A.]] |
| - | [[Category: Shafer, R | + | [[Category: Shafer, R H.]] |
[[Category: DXB]] | [[Category: DXB]] | ||
[[Category: MDA]] | [[Category: MDA]] | ||
| Line 23: | Line 23: | ||
[[Category: oligonucleotide]] | [[Category: oligonucleotide]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:57:39 2008'' |
Revision as of 09:57, 21 February 2008
|
4:2:1 MITHRAMYCIN:MG2+:D(ACCCGGGT)2 COMPLEX
Overview
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 Structure
1BP8 is a Protein complex structure of sequences from [1] with , and as ligands. Full crystallographic 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 Thu Feb 21 11:57:39 2008
Categories: Protein complex | Keniry, M A. | Owen, E A. | Shafer, R H. | DXB | MDA | MG | Dna | Mithramycin | Nmr | Oligonucleotide
