1i5v
From Proteopedia
(New page: 200px<br /><applet load="1i5v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i5v" /> '''SOLUTION STRUCTURE OF 2-(PYRIDO[1,2-E]PURIN-...) |
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| - | [[Image:1i5v.gif|left|200px]]<br /><applet load="1i5v" size=" | + | [[Image:1i5v.gif|left|200px]]<br /><applet load="1i5v" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1i5v" /> | caption="1i5v" /> | ||
'''SOLUTION STRUCTURE OF 2-(PYRIDO[1,2-E]PURIN-4-YL)AMINO-ETHANOL INTERCALATED IN THE DNA DUPLEX D(CGATCG)2'''<br /> | '''SOLUTION STRUCTURE OF 2-(PYRIDO[1,2-E]PURIN-4-YL)AMINO-ETHANOL INTERCALATED IN THE DNA DUPLEX D(CGATCG)2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The solution structure of the complex formed between d(CGATCG)(2) and | + | The solution structure of the complex formed between d(CGATCG)(2) and 2-(pyrido[1,2-e]purin-4-yl)amino-ethanol, a new antitumor drug under design, has been resolved using NMR spectroscopy and restrained molecular dynamic simulations. The drug molecule intercalates between each of the CpG dinucleotide steps with its side chain lying in the minor groove. Analysis of NMR data establishes a weak stacking interaction between the intercalated ligand and the DNA bases; however, the drug/DNA affinity is enhanced by a hydrogen bond between the hydroxyl group of the end of the intercalant side chain and the amide group of guanine G6. Unrestrained molecular dynamic simulations performed in a water box confirm the stability of the intercalation model. The structure of the intercalated complex enables insight into the structure-activity relationship, allowing rationalization of the design of new antineoplasic agents. |
==About this Structure== | ==About this Structure== | ||
| - | 1I5V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with PPZ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1I5V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=PPZ:'>PPZ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I5V OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Blackledge, M.]] | [[Category: Blackledge, M.]] | ||
| - | [[Category: Debousy, J | + | [[Category: Debousy, J C.]] |
[[Category: Favier, A.]] | [[Category: Favier, A.]] | ||
[[Category: Marion, D.]] | [[Category: Marion, D.]] | ||
| - | [[Category: Simorre, J | + | [[Category: Simorre, J P.]] |
[[Category: PPZ]] | [[Category: PPZ]] | ||
[[Category: double helix]] | [[Category: double helix]] | ||
[[Category: drug-dna complex]] | [[Category: drug-dna complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:08:19 2008'' |
Revision as of 11:08, 21 February 2008
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SOLUTION STRUCTURE OF 2-(PYRIDO[1,2-E]PURIN-4-YL)AMINO-ETHANOL INTERCALATED IN THE DNA DUPLEX D(CGATCG)2
Overview
The solution structure of the complex formed between d(CGATCG)(2) and 2-(pyrido[1,2-e]purin-4-yl)amino-ethanol, a new antitumor drug under design, has been resolved using NMR spectroscopy and restrained molecular dynamic simulations. The drug molecule intercalates between each of the CpG dinucleotide steps with its side chain lying in the minor groove. Analysis of NMR data establishes a weak stacking interaction between the intercalated ligand and the DNA bases; however, the drug/DNA affinity is enhanced by a hydrogen bond between the hydroxyl group of the end of the intercalant side chain and the amide group of guanine G6. Unrestrained molecular dynamic simulations performed in a water box confirm the stability of the intercalation model. The structure of the intercalated complex enables insight into the structure-activity relationship, allowing rationalization of the design of new antineoplasic agents.
About this Structure
1I5V is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Solution structure of 2-(pyrido[1,2-e]purin-4-yl)amino-ethanol intercalated in the DNA duplex d(CGATCG)2., Favier A, Blackledge M, Simorre JP, Crouzy S, Dabouis V, Gueiffier A, Marion D, Debouzy JC, Biochemistry. 2001 Jul 31;40(30):8717-26. PMID:11467931
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