1eg6

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(New page: 200px<br /><applet load="1eg6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eg6, resolution 2.00&Aring;" /> '''CRYSTAL STRUCTURE AN...)
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'''CRYSTAL STRUCTURE ANALYSIS OF D(CG(5-BRU)ACG) COMPLEXES TO A PHENAZINE'''<br />
'''CRYSTAL STRUCTURE ANALYSIS OF D(CG(5-BRU)ACG) COMPLEXES TO A PHENAZINE'''<br />
==Overview==
==Overview==
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The structure of the duplex d[CG(5-BrU)ACG](2) bound to, 9-bromophenazine-4-carboxamide has been solved through MAD phasing at 2.0, A resolution. It shows an unexpected and previously unreported, intercalation cavity stabilized by the drug and novel binding modes of, Co(2+) ions at certain guanine N7 sites. For the intercalation cavity the, terminal cytosine is rotated to pair with the guanine of a, symmetry-related duplex to create a pseudo-Holliday junction geometry, with two such cavities linked through the minor groove interactions of the, N2/N3 guanine sites at an angle of 40 degrees, creating a quadruplex-like, structure. The mode of binding of the drug is shown to be disordered, with, the major conformations showing the side chain bound to the N7 position of, adjacent guanines. The other end of the duplex exhibits a terminal base, fraying in the presence of Co(2+) ions linking symmetry-related guanines, causing the helices to intertwine through the minor groove. The, stabilization of the structure by the intercalating drug shows that this, class of compound may bind to DNA junctions as well as duplex DNA or to, strand-nicked DNA ('hemi-intercalated'), as in the cleavable complex. This, suggests a structural basis for the dual poisoning of topoisomerase I and, II enzymes by this family of drugs.
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The structure of the duplex d[CG(5-BrU)ACG](2) bound to 9-bromophenazine-4-carboxamide has been solved through MAD phasing at 2.0 A resolution. It shows an unexpected and previously unreported intercalation cavity stabilized by the drug and novel binding modes of Co(2+) ions at certain guanine N7 sites. For the intercalation cavity the terminal cytosine is rotated to pair with the guanine of a symmetry-related duplex to create a pseudo-Holliday junction geometry, with two such cavities linked through the minor groove interactions of the N2/N3 guanine sites at an angle of 40 degrees, creating a quadruplex-like structure. The mode of binding of the drug is shown to be disordered, with the major conformations showing the side chain bound to the N7 position of adjacent guanines. The other end of the duplex exhibits a terminal base fraying in the presence of Co(2+) ions linking symmetry-related guanines, causing the helices to intertwine through the minor groove. The stabilization of the structure by the intercalating drug shows that this class of compound may bind to DNA junctions as well as duplex DNA or to strand-nicked DNA ('hemi-intercalated'), as in the cleavable complex. This suggests a structural basis for the dual poisoning of topoisomerase I and II enzymes by this family of drugs.
==About this Structure==
==About this Structure==
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1EG6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with 3CO, BR and BFA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EG6 OCA].
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1EG6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=3CO:'>3CO</scene>, <scene name='pdbligand=BR:'>BR</scene> and <scene name='pdbligand=BFA:'>BFA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EG6 OCA].
==Reference==
==Reference==
Guanine specific binding at a DNA junction formed by d[CG(5-BrU)ACG](2) with a topoisomerase poison in the presence of Co(2+) ions., Thorpe JH, Hobbs JR, Todd AK, Denny WA, Charlton P, Cardin CJ, Biochemistry. 2000 Dec 12;39(49):15055-61. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11106483 11106483]
Guanine specific binding at a DNA junction formed by d[CG(5-BrU)ACG](2) with a topoisomerase poison in the presence of Co(2+) ions., Thorpe JH, Hobbs JR, Todd AK, Denny WA, Charlton P, Cardin CJ, Biochemistry. 2000 Dec 12;39(49):15055-61. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11106483 11106483]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Cardin, C.J.]]
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[[Category: Cardin, C J.]]
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[[Category: Denny, W.A.]]
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[[Category: Denny, W A.]]
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[[Category: Hobbs, J.R.]]
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[[Category: Hobbs, J R.]]
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[[Category: Thorpe, J.H.]]
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[[Category: Thorpe, J H.]]
[[Category: 3CO]]
[[Category: 3CO]]
[[Category: BFA]]
[[Category: BFA]]
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[[Category: major groove binding]]
[[Category: major groove binding]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:27:28 2008''

Revision as of 10:27, 21 February 2008

Image:1eg6.gif

1eg6, resolution 2.00Å

Drag the structure with the mouse to rotate

CRYSTAL STRUCTURE ANALYSIS OF D(CG(5-BRU)ACG) COMPLEXES TO A PHENAZINE

Overview

The structure of the duplex d[CG(5-BrU)ACG](2) bound to 9-bromophenazine-4-carboxamide has been solved through MAD phasing at 2.0 A resolution. It shows an unexpected and previously unreported intercalation cavity stabilized by the drug and novel binding modes of Co(2+) ions at certain guanine N7 sites. For the intercalation cavity the terminal cytosine is rotated to pair with the guanine of a symmetry-related duplex to create a pseudo-Holliday junction geometry, with two such cavities linked through the minor groove interactions of the N2/N3 guanine sites at an angle of 40 degrees, creating a quadruplex-like structure. The mode of binding of the drug is shown to be disordered, with the major conformations showing the side chain bound to the N7 position of adjacent guanines. The other end of the duplex exhibits a terminal base fraying in the presence of Co(2+) ions linking symmetry-related guanines, causing the helices to intertwine through the minor groove. The stabilization of the structure by the intercalating drug shows that this class of compound may bind to DNA junctions as well as duplex DNA or to strand-nicked DNA ('hemi-intercalated'), as in the cleavable complex. This suggests a structural basis for the dual poisoning of topoisomerase I and II enzymes by this family of drugs.

About this Structure

1EG6 is a Protein complex structure of sequences from [1] with , and as ligands. Full crystallographic information is available from OCA.

Reference

Guanine specific binding at a DNA junction formed by d[CG(5-BrU)ACG](2) with a topoisomerase poison in the presence of Co(2+) ions., Thorpe JH, Hobbs JR, Todd AK, Denny WA, Charlton P, Cardin CJ, Biochemistry. 2000 Dec 12;39(49):15055-61. PMID:11106483

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