1cyz
From Proteopedia
(New page: 200px<br /><applet load="1cyz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cyz" /> '''NMR STRUCTURE OF THE GAACTGGTTC/TRI-IMIDAZOL...) |
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| - | [[Image:1cyz.gif|left|200px]]<br /><applet load="1cyz" size=" | + | [[Image:1cyz.gif|left|200px]]<br /><applet load="1cyz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1cyz" /> | caption="1cyz" /> | ||
'''NMR STRUCTURE OF THE GAACTGGTTC/TRI-IMIDAZOLE POLYAMIDE COMPLEX'''<br /> | '''NMR STRUCTURE OF THE GAACTGGTTC/TRI-IMIDAZOLE POLYAMIDE COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The T:G mismatched base pair is associated with many genetic mutations. | + | The T:G mismatched base pair is associated with many genetic mutations. Understanding its biological consequences may be aided by studying the structural perturbation of DNA caused by a T:G base pair and by specific probing of the mismatch using small molecular ligands. We have shown previously that AR-1-144, a tri-imidazole (Im-Im-Im) minor groove binder, recognizes the sequence CCGG. NMR structural analysis of the symmetric 2:1 complex of AR-1-144 and GAACCGGTTC revealed that each AR-1-144 binds to four base pairs with the guanine N2 amino group forming a bifurcated hydrogen bond to a side-by-side Im/Im pair. We predicted that the free G-N2 amino group in a T:G wobble base pair can form two individual hydrogen bonds to a side-by-side Im/Im pair. Thus an Im/Im pair may be a good recognition motif for a T:G base pair in DNA. Cooperative and tight binding of an AR-1-144 homodimer to GAACTGGTTC permits a detailed structural analysis by 2D NOE NMR refinement and the refined structure confirms our prediction. Surprisingly, AR-1-144 does not bind to GAATCGGTTC. We further show that both the Im-Im-Im/Im-Py-Im heterodimer and the Im-Im-Im/Im-Im-Im homodimer bind strongly to the CACGGGTC + GACTCGTG duplex. These results together suggest that an Im/Im pair can specifically recognize a single T:G mismatch. Our results may be useful in future design of molecules (e.g. linked dimers) that can recognize a single T:G mismatch with specificity. |
==About this Structure== | ==About this Structure== | ||
| - | 1CYZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with AR1 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1CYZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=AR1:'>AR1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CYZ OCA]. |
==Reference== | ==Reference== | ||
Imidazole-imidazole pair as a minor groove recognition motif for T:G mismatched base pairs., Yang XL, Hubbard RB, Lee M, Tao ZF, Sugiyama H, Wang AH, Nucleic Acids Res. 1999 Nov 1;27(21):4183-90. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10518609 10518609] | Imidazole-imidazole pair as a minor groove recognition motif for T:G mismatched base pairs., Yang XL, Hubbard RB, Lee M, Tao ZF, Sugiyama H, Wang AH, Nucleic Acids Res. 1999 Nov 1;27(21):4183-90. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10518609 10518609] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: IV, R | + | [[Category: IV, R B.Hubbard.]] |
[[Category: Lee, M.]] | [[Category: Lee, M.]] | ||
[[Category: Sugiyama, H.]] | [[Category: Sugiyama, H.]] | ||
| - | [[Category: Tao, Z | + | [[Category: Tao, Z F.]] |
| - | [[Category: Wang, A | + | [[Category: Wang, A H.J.]] |
| - | [[Category: Yang, X | + | [[Category: Yang, X L.]] |
[[Category: AR1]] | [[Category: AR1]] | ||
[[Category: t:g recognized by im/im pair in the dna minor groove]] | [[Category: t:g recognized by im/im pair in the dna minor groove]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:11:09 2008'' |
Revision as of 10:11, 21 February 2008
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NMR STRUCTURE OF THE GAACTGGTTC/TRI-IMIDAZOLE POLYAMIDE COMPLEX
Overview
The T:G mismatched base pair is associated with many genetic mutations. Understanding its biological consequences may be aided by studying the structural perturbation of DNA caused by a T:G base pair and by specific probing of the mismatch using small molecular ligands. We have shown previously that AR-1-144, a tri-imidazole (Im-Im-Im) minor groove binder, recognizes the sequence CCGG. NMR structural analysis of the symmetric 2:1 complex of AR-1-144 and GAACCGGTTC revealed that each AR-1-144 binds to four base pairs with the guanine N2 amino group forming a bifurcated hydrogen bond to a side-by-side Im/Im pair. We predicted that the free G-N2 amino group in a T:G wobble base pair can form two individual hydrogen bonds to a side-by-side Im/Im pair. Thus an Im/Im pair may be a good recognition motif for a T:G base pair in DNA. Cooperative and tight binding of an AR-1-144 homodimer to GAACTGGTTC permits a detailed structural analysis by 2D NOE NMR refinement and the refined structure confirms our prediction. Surprisingly, AR-1-144 does not bind to GAATCGGTTC. We further show that both the Im-Im-Im/Im-Py-Im heterodimer and the Im-Im-Im/Im-Im-Im homodimer bind strongly to the CACGGGTC + GACTCGTG duplex. These results together suggest that an Im/Im pair can specifically recognize a single T:G mismatch. Our results may be useful in future design of molecules (e.g. linked dimers) that can recognize a single T:G mismatch with specificity.
About this Structure
1CYZ is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Imidazole-imidazole pair as a minor groove recognition motif for T:G mismatched base pairs., Yang XL, Hubbard RB, Lee M, Tao ZF, Sugiyama H, Wang AH, Nucleic Acids Res. 1999 Nov 1;27(21):4183-90. PMID:10518609
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