1agl
From Proteopedia
(New page: 200px<br /><applet load="1agl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1agl, resolution 2.200Å" /> '''STRUCTURE OF A DNA-...) |
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| - | [[Image:1agl.gif|left|200px]]<br /><applet load="1agl" size=" | + | [[Image:1agl.gif|left|200px]]<br /><applet load="1agl" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1agl, resolution 2.200Å" /> | caption="1agl, resolution 2.200Å" /> | ||
'''STRUCTURE OF A DNA-BISDAUNOMYCIN COMPLEX'''<br /> | '''STRUCTURE OF A DNA-BISDAUNOMYCIN COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The application of detailed structural data bases has now culminated in | + | The application of detailed structural data bases has now culminated in the successful design of a new generation of bisanthracyclines that form ultratight DNA complexes [Chaires, J. B., Leng, F., Przewloka, T., Fokt, I., Ling, Y. H., Perez-Soler, R., & Priebe, W. (1997) J. Med. Chem. 40, 261-266]. Daunomycin dimers were designed to bind to DNA in complexes resembling those of monomers intercalated at adjacent sites. The goal of the work described here was to determine, with X-ray crystallography, if a potent member of this newly designed and synthesized class of bisanthracyclines (WP631) binds as intended. WP631 is composed of two daunomycin molecules, linked N3' to N3' by a xylyl group. We have solved the 2.2 A X-ray crystal structure of a complex of WP631 bound to [d(CGATCG)]2. We demonstrate, on a detailed molecular level, that the WP631 design strategy is a success. The structures of WP631 and two daunomycin molecules bound to [d(CGATCG)]2 provide the unprecedented opportunity for detailed comparison of mono- and bis-intercalated complexes of the same chromophore, allowing us to distinguish effects of mono-intercalation from those of bis-intercalation. Differences are focused primarily in the centers of the complexes. DNA unwinding and other helical distortions propagate more efficiently to the center of the WP631 complex than to the center of the daunomycin complex. |
==About this Structure== | ==About this Structure== | ||
| - | 1AGL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with BDA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1AGL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=BDA:'>BDA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AGL OCA]. |
==Reference== | ==Reference== | ||
Structure of a DNA-bisdaunomycin complex., Hu GG, Shui X, Leng F, Priebe W, Chaires JB, Williams LD, Biochemistry. 1997 May 20;36(20):5940-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9166763 9166763] | Structure of a DNA-bisdaunomycin complex., Hu GG, Shui X, Leng F, Priebe W, Chaires JB, Williams LD, Biochemistry. 1997 May 20;36(20):5940-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9166763 9166763] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Chaires, J | + | [[Category: Chaires, J B.]] |
| - | [[Category: Hu, G | + | [[Category: Hu, G G.]] |
[[Category: Leng, F.]] | [[Category: Leng, F.]] | ||
[[Category: Priebe, W.]] | [[Category: Priebe, W.]] | ||
[[Category: Shui, X.]] | [[Category: Shui, X.]] | ||
| - | [[Category: Williams, L | + | [[Category: Williams, L D.]] |
[[Category: BDA]] | [[Category: BDA]] | ||
[[Category: complexed with drug]] | [[Category: complexed with drug]] | ||
| Line 23: | Line 23: | ||
[[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 11:44:16 2008'' |
Revision as of 09:44, 21 February 2008
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STRUCTURE OF A DNA-BISDAUNOMYCIN COMPLEX
Overview
The application of detailed structural data bases has now culminated in the successful design of a new generation of bisanthracyclines that form ultratight DNA complexes [Chaires, J. B., Leng, F., Przewloka, T., Fokt, I., Ling, Y. H., Perez-Soler, R., & Priebe, W. (1997) J. Med. Chem. 40, 261-266]. Daunomycin dimers were designed to bind to DNA in complexes resembling those of monomers intercalated at adjacent sites. The goal of the work described here was to determine, with X-ray crystallography, if a potent member of this newly designed and synthesized class of bisanthracyclines (WP631) binds as intended. WP631 is composed of two daunomycin molecules, linked N3' to N3' by a xylyl group. We have solved the 2.2 A X-ray crystal structure of a complex of WP631 bound to [d(CGATCG)]2. We demonstrate, on a detailed molecular level, that the WP631 design strategy is a success. The structures of WP631 and two daunomycin molecules bound to [d(CGATCG)]2 provide the unprecedented opportunity for detailed comparison of mono- and bis-intercalated complexes of the same chromophore, allowing us to distinguish effects of mono-intercalation from those of bis-intercalation. Differences are focused primarily in the centers of the complexes. DNA unwinding and other helical distortions propagate more efficiently to the center of the WP631 complex than to the center of the daunomycin complex.
About this Structure
1AGL is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Structure of a DNA-bisdaunomycin complex., Hu GG, Shui X, Leng F, Priebe W, Chaires JB, Williams LD, Biochemistry. 1997 May 20;36(20):5940-6. PMID:9166763
Page seeded by OCA on Thu Feb 21 11:44:16 2008
