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1b0s
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(New page: 200px<br /><applet load="1b0s" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b0s" /> '''BINDING OF AR-1-144, A TRI-IMIDAZOLE DNA MIN...)
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Revision as of 21:27, 24 November 2007
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BINDING OF AR-1-144, A TRI-IMIDAZOLE DNA MINOR GROOVE BINDER, TO CCGG SEQUENCE ANALYZED BY NMR SPECTROSCOPY
Overview
The interactions of, N-[2-(dimethylamino)ethyl]-1-methyl-4-[1-methyl-4-[4-formamido-1-meth, ylimidazole-2-carboxamido]imidazole-2-carboxamido]imidazole-2-c arboxa, mide (AR-1-144), a tri-imidazole polyamide minor groove binder, with DNA, have been investigated by NMR and CD spectroscopy. A series of DNA, oligonucleotides with a C/G-containing four-bp core, i.e. CCGG, CGCG, GGCC, and GCGC, have been titrated with AR-1-144 at different ratios., AR-1-144 favors the CCGG sequence. The flanking sequence of the CCGG core, also influences the binding preference, with a C or T being favored on the, 3'-side of the CCGG core. The three-dimensional structure of the symmetric, 2:1 side-by-side complex of AR-1-144 and GAACCGGTTC, determined by, NOE-constrained NMR refinement, reveals that each AR-1-144 binds to four, base pairs, i.e. at C5-G6-G7-T8, with every amide-imidazole unit forming, two potential hydrogen bonds with DNA. The same DNA binding preference of, AR-1-144 was also confirmed by circular dichroism spectroscopy, indicating, that the DNA binding preference of AR-1-144 is independent of, concentration. The cooperative binding of an AR-1-144 homodimer to the, (purine)CCGG(pyrimidine) core sequence appears to be weaker than that of, the distamycin A homodimer to A/T sequences, most likely due to the, diminished hydrophobic interactions between AR-1-144 and DNA. Our results, are consistent with previous footprinting data and explain the binding, pattern found in the crystal structure of a di-imidazole drug bound to, CATGGCCATG.
About this Structure
1B0S is a Protein complex structure of sequences from [1] with AR1 as ligand. Full crystallographic information is available from OCA.
Reference
Binding of AR-1-144, a tri-imidazole DNA minor groove binder, to CCGG sequence analyzed by NMR spectroscopy., Yang XL, Kaenzig C, Lee M, Wang AH, Eur J Biochem. 1999 Aug;263(3):646-55. PMID:10469127
Page seeded by OCA on Sat Nov 24 23:35:11 2007
