1b0s
From Proteopedia
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|PDB= 1b0s |SIZE=350|CAPTION= <scene name='initialview01'>1b0s</scene> | |PDB= 1b0s |SIZE=350|CAPTION= <scene name='initialview01'>1b0s</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=AR1:(2-{[4-({4-[(4-FORMYLAMINO-1-METHYL-1H-IMIDAZOLE-2-CARBONYL)-AMINO]-1-METHYL-1H-IMIDAZOLE-2-CARBONYL}-AMINO)-1-METHYL-1H-IMIDAZOLE-2-CARBONYL]-AMINO}-ETHYL)-DIMETHYL-AMMONIUM'>AR1</scene> | + | |LIGAND= <scene name='pdbligand=AR1:(2-{[4-({4-[(4-FORMYLAMINO-1-METHYL-1H-IMIDAZOLE-2-CARBONYL)-AMINO]-1-METHYL-1H-IMIDAZOLE-2-CARBONYL}-AMINO)-1-METHYL-1H-IMIDAZOLE-2-CARBONYL]-AMINO}-ETHYL)-DIMETHYL-AMMONIUM'>AR1</scene>, <scene name='pdbligand=DA:2'-DEOXYADENOSINE-5'-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2'-DEOXYCYTIDINE-5'-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5'-MONOPHOSPHATE'>DT</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1b0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b0s OCA], [http://www.ebi.ac.uk/pdbsum/1b0s PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1b0s RCSB]</span> | ||
}} | }} | ||
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[[Category: Wang, A H.J.]] | [[Category: Wang, A H.J.]] | ||
[[Category: Yang, X L.]] | [[Category: Yang, X L.]] | ||
| - | [[Category: AR1]] | ||
[[Category: anticancer drug]] | [[Category: anticancer drug]] | ||
[[Category: dna structure]] | [[Category: dna structure]] | ||
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[[Category: sequence specific recognition]] | [[Category: sequence specific recognition]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:51:20 2008'' |
Revision as of 15:51, 30 March 2008
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| Ligands: | , , , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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]. 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
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