1CYZ

NMR STRUCTURE OF THE GAACTGGTTC/TRI-IMIDAZOLE POLYAMIDE COMPLEX

Summary for 1CYZ

• Entry DOI: 10.2210/pdb1cyz/pdb
• Related: 1B0S
• NMR Information: BMRB: 4392
• Descriptor: 5'-D(*GP*AP*AP*CP*TP*GP*GP*TP*TP*C)-3', (2-{[4-({4-[(4-FORMYLAMINO-1-METHYL-1H-IMIDAZOLE-2-CARBONYL)-AMINO]-1-METHYL-1H-IMIDAZOLE-2-CARBONYL}-AMINO)-1-METHYL-1 H-IMIDAZOLE-2-CARBONYL]-AMINO}-ETHYL)-DIMETHYL-AMMONIUM (2 entities in total)
• Functional Keywords: t:g recognized by im/im pair in the dna minor groove, dna
• Total number of polymer chains: 2
• Total formula weight: 7093.05

Authors

Yang, X.-L.,Hubbard IV, R.B.,Lee, M.,Tao, Z.-F.,Sugiyama, H.,Wang, A.H.-J. (deposition date: 1999-08-31, release date: 1999-09-14, Last modification date: 2024-05-22)

Primary citation

Yang, X.-L.,Hubbard IV, R.B.,Lee, M.,Tao, Z.-F.,Sugiyama, H.,Wang, A.H.-J.
Imidazole-imidazole pair as a minor groove recognition motif for T:G mismatched base pairs
Nucleic Acids Res., 27:4183-4190, 1999

PubMed Abstract: 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.

PubMed: 10518609
DOI: 10.1093/nar/27.21.4183

Experimental method

SOLUTION NMR