1da0
From Proteopedia
(New page: 200px<br /><applet load="1da0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1da0, resolution 1.500Å" /> '''DNA-DRUG INTERACTIO...) |
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| - | [[Image:1da0.gif|left|200px]]<br /><applet load="1da0" size=" | + | [[Image:1da0.gif|left|200px]]<br /><applet load="1da0" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1da0, resolution 1.500Å" /> | caption="1da0, resolution 1.500Å" /> | ||
'''DNA-DRUG INTERACTIONS: THE CRYSTAL STRUCTURE OF D(CGATCG) COMPLEXED WITH DAUNOMYCIN'''<br /> | '''DNA-DRUG INTERACTIONS: THE CRYSTAL STRUCTURE OF D(CGATCG) COMPLEXED WITH DAUNOMYCIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of a d(CGATCG)-daunomycin complex has been determined by | + | The structure of a d(CGATCG)-daunomycin complex has been determined by single crystal X-ray diffraction techniques. Refinement, with the location of 40 solvent molecules, using data up to 1.5 A, converged with a final crystallographic residual, R = 0.25 (RW = 0.22). The tetragonal crystals are in space group P4(1)2(1)2, with cell dimensions of a = 27.98 A and c = 52.87 A. The self-complementary d(CGATCG) forms a distorted right-handed helix with a daunomycin molecule intercalated at each d(CpG) step. The daunomycin aglycon chromophore is oriented at right-angles to the long axis of the DNA base-pairs. This head-on intercalation is stabilized by direct hydrogen bonds and indirectly via solvent-mediated, hydrogen-bonding interactions between the chromophore and its intercalation site base-pairs. The cyclohexene ring and amino sugar substituent lie in the minor groove. The amino sugar N-3' forms a hydrogen bond with O-2 of the next neighbouring thymine. This electrostatic interaction helps position the sugar in a way that results in extensive van der Waals contacts between the drug and the DNA. There is no interaction between daunosamine and the DNA sugar-phosphate backbone. We present full experimental details and all relevant conformational parameters, and use the comparison with a d(CGTACG)-daunomycin complex to rationalize some neighbouring sequence effects involved in daunomycin binding. |
==About this Structure== | ==About this Structure== | ||
| - | 1DA0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with DM1 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1DA0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=DM1:'>DM1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DA0 OCA]. |
==Reference== | ==Reference== | ||
DNA-drug interactions. The crystal structure of d(CGATCG) complexed with daunomycin., Moore MH, Hunter WN, d'Estaintot BL, Kennard O, J Mol Biol. 1989 Apr 20;206(4):693-705. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=2738914 2738914] | DNA-drug interactions. The crystal structure of d(CGATCG) complexed with daunomycin., Moore MH, Hunter WN, d'Estaintot BL, Kennard O, J Mol Biol. 1989 Apr 20;206(4):693-705. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=2738914 2738914] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Estaintot, B | + | [[Category: Estaintot, B Langlois D.]] |
| - | [[Category: Hunter, W | + | [[Category: Hunter, W N.]] |
[[Category: Kennard, O.]] | [[Category: Kennard, O.]] | ||
| - | [[Category: Moore, M | + | [[Category: Moore, M H.]] |
[[Category: DM1]] | [[Category: DM1]] | ||
[[Category: complexed with drug]] | [[Category: complexed with drug]] | ||
| Line 21: | Line 21: | ||
[[Category: right handed dna]] | [[Category: right handed dna]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:14:30 2008'' |
Revision as of 10:14, 21 February 2008
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DNA-DRUG INTERACTIONS: THE CRYSTAL STRUCTURE OF D(CGATCG) COMPLEXED WITH DAUNOMYCIN
Overview
The structure of a d(CGATCG)-daunomycin complex has been determined by single crystal X-ray diffraction techniques. Refinement, with the location of 40 solvent molecules, using data up to 1.5 A, converged with a final crystallographic residual, R = 0.25 (RW = 0.22). The tetragonal crystals are in space group P4(1)2(1)2, with cell dimensions of a = 27.98 A and c = 52.87 A. The self-complementary d(CGATCG) forms a distorted right-handed helix with a daunomycin molecule intercalated at each d(CpG) step. The daunomycin aglycon chromophore is oriented at right-angles to the long axis of the DNA base-pairs. This head-on intercalation is stabilized by direct hydrogen bonds and indirectly via solvent-mediated, hydrogen-bonding interactions between the chromophore and its intercalation site base-pairs. The cyclohexene ring and amino sugar substituent lie in the minor groove. The amino sugar N-3' forms a hydrogen bond with O-2 of the next neighbouring thymine. This electrostatic interaction helps position the sugar in a way that results in extensive van der Waals contacts between the drug and the DNA. There is no interaction between daunosamine and the DNA sugar-phosphate backbone. We present full experimental details and all relevant conformational parameters, and use the comparison with a d(CGTACG)-daunomycin complex to rationalize some neighbouring sequence effects involved in daunomycin binding.
About this Structure
1DA0 is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
DNA-drug interactions. The crystal structure of d(CGATCG) complexed with daunomycin., Moore MH, Hunter WN, d'Estaintot BL, Kennard O, J Mol Biol. 1989 Apr 20;206(4):693-705. PMID:2738914
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