1n37
From Proteopedia
(New page: 200px<br /><applet load="1n37" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n37" /> '''NMR Solution Structure of the Anthracycline ...) |
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| - | [[Image:1n37.gif|left|200px]]<br /><applet load="1n37" size=" | + | [[Image:1n37.gif|left|200px]]<br /><applet load="1n37" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1n37" /> | caption="1n37" /> | ||
'''NMR Solution Structure of the Anthracycline Respinomycin D Intercalation Complex with a Double Stranded DNA Molecule (AGACGTCT)2'''<br /> | '''NMR Solution Structure of the Anthracycline Respinomycin D Intercalation Complex with a Double Stranded DNA Molecule (AGACGTCT)2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Respinomycin D is a member of the anthracycline family of antitumour | + | Respinomycin D is a member of the anthracycline family of antitumour antibiotics that interact with double stranded DNA through intercalation. The clinical agents daunomycin and doxorubicin are the most well-studied of this class but have a relatively simple molecular architecture in which the pendant daunosamine sugar resides in the DNA minor groove. Respinomycin D, which belongs to the nogalamycin group of anthracyclines, possesses additional sugar residues at either end of the aglycone chromophore that modulate the biological activity but whose role in molecular recognition is unknown. We report the NMR structure of the respinomycin D-d(AGACGTCT)2 complex in solution derived from NOE restraints and molecular dynamics simulations. We show that the drug threads through the DNA double helix forming stabilising interactions in both the major and minor groove, the latter through a different binding geometry to that previously reported. The bicycloaminoglucose sugar resides in the major groove and makes specific contacts with guanine at the 5'-CpG intercalation site, however, the disaccharide attached at the C4 position plays little part in drug binding and DNA recognition and is largely solvent exposed. |
==About this Structure== | ==About this Structure== | ||
| - | 1N37 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with RSD as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1N37 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=RSD:'>RSD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N37 OCA]. |
==Reference== | ==Reference== | ||
DNA recognition by the anthracycline antibiotic respinomycin D: NMR structure of the intercalation complex with d(AGACGTCT)2., Searle MS, Maynard AJ, Williams HE, Org Biomol Chem. 2003 Jan 7;1(1):60-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12929391 12929391] | DNA recognition by the anthracycline antibiotic respinomycin D: NMR structure of the intercalation complex with d(AGACGTCT)2., Searle MS, Maynard AJ, Williams HE, Org Biomol Chem. 2003 Jan 7;1(1):60-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12929391 12929391] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Maynard, A | + | [[Category: Maynard, A J.]] |
| - | [[Category: Searle, M | + | [[Category: Searle, M S.]] |
| - | [[Category: Williams, H | + | [[Category: Williams, H E.L.]] |
[[Category: RSD]] | [[Category: RSD]] | ||
[[Category: anthracycline antibiotcs]] | [[Category: anthracycline antibiotcs]] | ||
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[[Category: respinomycin d]] | [[Category: respinomycin d]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:01:46 2008'' |
Revision as of 12:01, 21 February 2008
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NMR Solution Structure of the Anthracycline Respinomycin D Intercalation Complex with a Double Stranded DNA Molecule (AGACGTCT)2
Overview
Respinomycin D is a member of the anthracycline family of antitumour antibiotics that interact with double stranded DNA through intercalation. The clinical agents daunomycin and doxorubicin are the most well-studied of this class but have a relatively simple molecular architecture in which the pendant daunosamine sugar resides in the DNA minor groove. Respinomycin D, which belongs to the nogalamycin group of anthracyclines, possesses additional sugar residues at either end of the aglycone chromophore that modulate the biological activity but whose role in molecular recognition is unknown. We report the NMR structure of the respinomycin D-d(AGACGTCT)2 complex in solution derived from NOE restraints and molecular dynamics simulations. We show that the drug threads through the DNA double helix forming stabilising interactions in both the major and minor groove, the latter through a different binding geometry to that previously reported. The bicycloaminoglucose sugar resides in the major groove and makes specific contacts with guanine at the 5'-CpG intercalation site, however, the disaccharide attached at the C4 position plays little part in drug binding and DNA recognition and is largely solvent exposed.
About this Structure
1N37 is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
DNA recognition by the anthracycline antibiotic respinomycin D: NMR structure of the intercalation complex with d(AGACGTCT)2., Searle MS, Maynard AJ, Williams HE, Org Biomol Chem. 2003 Jan 7;1(1):60-6. PMID:12929391
Page seeded by OCA on Thu Feb 21 14:01:46 2008
