1pqq
From Proteopedia
(New page: 200px<br /><applet load="1pqq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pqq" /> '''NMR Structure of a Cyclic Polyamide-DNA Comp...) |
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'''NMR Structure of a Cyclic Polyamide-DNA Complex'''<br /> | '''NMR Structure of a Cyclic Polyamide-DNA Complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The solution structure of a cyclic polyamide ligand complexed to a DNA | + | The solution structure of a cyclic polyamide ligand complexed to a DNA oligomer, derived from NMR restrained molecular mechanics, is presented. The polyamide, cyclo-gamma-ImPyPy-gamma-PyPyPy-, binds to target DNA with a nanomolar dissociation constant as characterized by quantitative footprinting previously reported. 2D (1)H NMR data were used to generate distance restraints defining the structure of this cyclic polyamide with the DNA duplex d(5'-GCCTGTTAGCG-3'):d(5'-CGCTAACAGGC-3'). Data interpretation used complete relaxation matrix analysis of the NOESY cross-peak intensities with the program MARDIGRAS. The NMR-based distance restraints (276 total) were applied in restrained molecular dynamics calculations using a solvent model, yielding structures with an rmsd for the ligand and binding site of approximately 1 A. The resulting structures indicate some distortion of the DNA in the binding site. The constraints from cyclization lead to altered stacking of the rings in the halves of the cyclic ligand relative to unlinked complexes. Despite this, the interactions with DNA are very similar to what has been found in unlinked complexes. Measurements of ligand amide and DNA imino proton exchange rates indicate very slow dissociation of the ligand and show that the DNA can undergo opening fluctuations while the ligand is bound although the presence of the ligand decreases their frequency relative to the free DNA. |
==About this Structure== | ==About this Structure== | ||
| - | 1PQQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with CYE as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1PQQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=CYE:'>CYE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PQQ OCA]. |
==Reference== | ==Reference== | ||
NMR structure of a cyclic polyamide-DNA complex., Zhang Q, Dwyer TJ, Tsui V, Case DA, Cho J, Dervan PB, Wemmer DE, J Am Chem Soc. 2004 Jun 30;126(25):7958-66. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15212545 15212545] | NMR structure of a cyclic polyamide-DNA complex., Zhang Q, Dwyer TJ, Tsui V, Case DA, Cho J, Dervan PB, Wemmer DE, J Am Chem Soc. 2004 Jun 30;126(25):7958-66. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15212545 15212545] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Case, D | + | [[Category: Case, D A.]] |
[[Category: Cho, J.]] | [[Category: Cho, J.]] | ||
| - | [[Category: Dervan, P | + | [[Category: Dervan, P B.]] |
| - | [[Category: Dwyer, T | + | [[Category: Dwyer, T J.]] |
[[Category: Tsui, V.]] | [[Category: Tsui, V.]] | ||
| - | [[Category: Wemmer, D | + | [[Category: Wemmer, D E.]] |
[[Category: Zhang, Q.]] | [[Category: Zhang, Q.]] | ||
[[Category: CYE]] | [[Category: CYE]] | ||
[[Category: dna]] | [[Category: dna]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:31:33 2008'' |
Revision as of 12:31, 21 February 2008
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NMR Structure of a Cyclic Polyamide-DNA Complex
Overview
The solution structure of a cyclic polyamide ligand complexed to a DNA oligomer, derived from NMR restrained molecular mechanics, is presented. The polyamide, cyclo-gamma-ImPyPy-gamma-PyPyPy-, binds to target DNA with a nanomolar dissociation constant as characterized by quantitative footprinting previously reported. 2D (1)H NMR data were used to generate distance restraints defining the structure of this cyclic polyamide with the DNA duplex d(5'-GCCTGTTAGCG-3'):d(5'-CGCTAACAGGC-3'). Data interpretation used complete relaxation matrix analysis of the NOESY cross-peak intensities with the program MARDIGRAS. The NMR-based distance restraints (276 total) were applied in restrained molecular dynamics calculations using a solvent model, yielding structures with an rmsd for the ligand and binding site of approximately 1 A. The resulting structures indicate some distortion of the DNA in the binding site. The constraints from cyclization lead to altered stacking of the rings in the halves of the cyclic ligand relative to unlinked complexes. Despite this, the interactions with DNA are very similar to what has been found in unlinked complexes. Measurements of ligand amide and DNA imino proton exchange rates indicate very slow dissociation of the ligand and show that the DNA can undergo opening fluctuations while the ligand is bound although the presence of the ligand decreases their frequency relative to the free DNA.
About this Structure
1PQQ is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
NMR structure of a cyclic polyamide-DNA complex., Zhang Q, Dwyer TJ, Tsui V, Case DA, Cho J, Dervan PB, Wemmer DE, J Am Chem Soc. 2004 Jun 30;126(25):7958-66. PMID:15212545
Page seeded by OCA on Thu Feb 21 14:31:33 2008
Categories: Protein complex | Case, D A. | Cho, J. | Dervan, P B. | Dwyer, T J. | Tsui, V. | Wemmer, D E. | Zhang, Q. | CYE | Dna
