Imidazole-imidazole pair as a minor groove recognition motif for T:G mismatched base pairs

Xiang Lei Yang, Richard B. Hubbard IV, Moses Lee, Zhi Fu Tao, Hiroshi Sugiyama, Andrew H.J. Wang

研究成果: 雜誌貢獻文章同行評審

47 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)4183-4190
頁數8
期刊Nucleic Acids Research
27
發行號21
DOIs
出版狀態已發佈 - 11月 1 1999
對外發佈

ASJC Scopus subject areas

  • 遺傳學

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