1cyz: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| (12 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==NMR STRUCTURE OF THE GAACTGGTTC/TRI-IMIDAZOLE POLYAMIDE COMPLEX== | ||
<StructureSection load='1cyz' size='340' side='right'caption='[[1cyz]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1cyz]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CYZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CYZ FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR1:(2-{[4-({4-[(4-FORMYLAMINO-1-METHYL-1H-IMIDAZOLE-2-CARBONYL)-AMINO]-1-METHYL-1H-IMIDAZOLE-2-CARBONYL}-AMINO)-1-METHYL-1H-IMIDAZOLE-2-CARBONYL]-AMINO}-ETHYL)-DIMETHYL-AMMONIUM'>AR1</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1cyz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cyz OCA], [https://pdbe.org/1cyz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cyz RCSB], [https://www.ebi.ac.uk/pdbsum/1cyz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cyz ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | 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. | ||
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<ref>PMID:10518609</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: | <div class="pdbe-citations 1cyz" style="background-color:#fffaf0;"></div> | ||
[[Category: IV | == References == | ||
[[Category: Lee | <references/> | ||
[[Category: Sugiyama | __TOC__ | ||
[[Category: Tao | </StructureSection> | ||
[[Category: Wang | [[Category: Large Structures]] | ||
[[Category: Yang | [[Category: Hubbard IV RB]] | ||
[[Category: Lee M]] | |||
[[Category: Sugiyama H]] | |||
[[Category: Tao Z-F]] | |||
[[Category: Wang AH-J]] | |||
[[Category: Yang X-L]] | |||
Latest revision as of 11:41, 22 November 2023
NMR STRUCTURE OF THE GAACTGGTTC/TRI-IMIDAZOLE POLYAMIDE COMPLEX
| ||||||||||||
