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| | {{STRUCTURE_1b0s| PDB=1b0s | SCENE= }} | | {{STRUCTURE_1b0s| PDB=1b0s | SCENE= }} |
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| - | '''BINDING OF AR-1-144, A TRI-IMIDAZOLE DNA MINOR GROOVE BINDER, TO CCGG SEQUENCE ANALYZED BY NMR SPECTROSCOPY'''
| + | ===BINDING OF AR-1-144, A TRI-IMIDAZOLE DNA MINOR GROOVE BINDER, TO CCGG SEQUENCE ANALYZED BY NMR SPECTROSCOPY=== |
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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_10469127}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10469127 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10469127}} |
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| | ==About this Structure== | | ==About this Structure== |
| - | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B0S OCA]. | + | Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B0S OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: Drug design]] | | [[Category: Drug design]] |
| | [[Category: Sequence specific recognition]] | | [[Category: Sequence specific recognition]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:55:54 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 18:00:10 2008'' |
Revision as of 15:00, 30 June 2008
Template:STRUCTURE 1b0s
BINDING OF AR-1-144, A TRI-IMIDAZOLE DNA MINOR GROOVE BINDER, TO CCGG SEQUENCE ANALYZED BY NMR SPECTROSCOPY
Template:ABSTRACT PUBMED 10469127
About this Structure
Full experimental 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 Mon Jun 30 18:00:10 2008
