1cyz

From Proteopedia

Revision as of 23:59, 24 November 2007

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 AR1 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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