1eki
From Proteopedia
(New page: 200px<br /><applet load="1eki" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eki" /> '''AVERAGE SOLUTION STRUCTURE OF D(TTGGCCAA)2 B...) |
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| - | [[Image:1eki.gif|left|200px]]<br /><applet load="1eki" size=" | + | [[Image:1eki.gif|left|200px]]<br /><applet load="1eki" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1eki" /> | caption="1eki" /> | ||
'''AVERAGE SOLUTION STRUCTURE OF D(TTGGCCAA)2 BOUND TO CHROMOMYCIN-A3 AND COBALT'''<br /> | '''AVERAGE SOLUTION STRUCTURE OF D(TTGGCCAA)2 BOUND TO CHROMOMYCIN-A3 AND COBALT'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The drug chromomycin-A(3) binds to the minor groove of DNA and | + | BACKGROUND: The drug chromomycin-A(3) binds to the minor groove of DNA and requires a divalent metal ion for complex formation. (1)H, (31)P and (13)C pseudocontact shifts occurring in the presence of a tightly bound divalent cobalt ion in the complex between d(TTGGCCAA)(2) and chromomycin-A(3) have been used to determine the structure of the complex. The accuracy of the structure was verified by validation with nuclear Overhauser enhancements (NOEs) and J-coupling constants not used in the structure calculation. RESULTS: The final structure was determined to 0.7 A resolution. The structure was compared with a structure obtained in an earlier study using NOEs, in order to assess the accuracy of NOEs in giving global structural information for a DNA complex. Although some basic features of the structures agreed, they differed substantially in the fine structural details and in the DNA axis curvature generated by the drug. The distortion of base-pair planarity that was observed in the NOE structure was not seen in our structure. Differences in drug orientation and hydrogen bonding also occurred. The curvature and elongation of the DNA that was obtained previously was not found to occur in our study. CONCLUSIONS: The use of pseudocontact shifts has enabled us to obtain a high-precision global structure of the chromomycin-DNA complex, which provides an accurate template on which to consider targeting minor groove binding drugs. The effect of such binding is not propagated far along the helix but is restricted to a local kink in the axis that reverts to its original direction within four base pairs. |
==About this Structure== | ==About this Structure== | ||
| - | 1EKI is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with CO and DXB as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1EKI is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=CO:'>CO</scene> and <scene name='pdbligand=DXB:'>DXB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EKI OCA]. |
==Reference== | ==Reference== | ||
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[[Category: drug bound in the minor groove of dna]] | [[Category: drug bound in the minor groove of dna]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:28:44 2008'' |
Revision as of 10:28, 21 February 2008
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AVERAGE SOLUTION STRUCTURE OF D(TTGGCCAA)2 BOUND TO CHROMOMYCIN-A3 AND COBALT
Overview
BACKGROUND: The drug chromomycin-A(3) binds to the minor groove of DNA and requires a divalent metal ion for complex formation. (1)H, (31)P and (13)C pseudocontact shifts occurring in the presence of a tightly bound divalent cobalt ion in the complex between d(TTGGCCAA)(2) and chromomycin-A(3) have been used to determine the structure of the complex. The accuracy of the structure was verified by validation with nuclear Overhauser enhancements (NOEs) and J-coupling constants not used in the structure calculation. RESULTS: The final structure was determined to 0.7 A resolution. The structure was compared with a structure obtained in an earlier study using NOEs, in order to assess the accuracy of NOEs in giving global structural information for a DNA complex. Although some basic features of the structures agreed, they differed substantially in the fine structural details and in the DNA axis curvature generated by the drug. The distortion of base-pair planarity that was observed in the NOE structure was not seen in our structure. Differences in drug orientation and hydrogen bonding also occurred. The curvature and elongation of the DNA that was obtained previously was not found to occur in our study. CONCLUSIONS: The use of pseudocontact shifts has enabled us to obtain a high-precision global structure of the chromomycin-DNA complex, which provides an accurate template on which to consider targeting minor groove binding drugs. The effect of such binding is not propagated far along the helix but is restricted to a local kink in the axis that reverts to its original direction within four base pairs.
About this Structure
1EKI is a Protein complex structure of sequences from [1] with and as ligands. Full crystallographic information is available from OCA.
Reference
A high-resolution structure of a DNA-chromomycin-Co(II) complex determined from pseudocontact shifts in nuclear magnetic resonance., Gochin M, Structure. 2000 Apr 15;8(4):441-52. PMID:10801486
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