2fjv
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2fjv.gif|left|200px]] | [[Image:2fjv.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2fjv", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_2fjv| PDB=2fjv | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''RT29 Bound to D(CTTAATTCGAATTAAG) in complex with MMLV RT Catalytic Fragment''' | '''RT29 Bound to D(CTTAATTCGAATTAAG) in complex with MMLV RT Catalytic Fragment''' | ||
| Line 28: | Line 25: | ||
[[Category: Georgiadis, M M.]] | [[Category: Georgiadis, M M.]] | ||
[[Category: Goodwin, K D.]] | [[Category: Goodwin, K D.]] | ||
| - | [[Category: | + | [[Category: Benzamidazole]] |
| - | [[Category: | + | [[Category: Drug-dna complex]] |
| - | [[Category: | + | [[Category: Mmlv rt]] |
| - | [[Category: | + | [[Category: Protein-dna complex,water-mediated interaction]] |
| - | [[Category: | + | [[Category: Rt29]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:58:55 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 00:58, 4 May 2008
RT29 Bound to D(CTTAATTCGAATTAAG) in complex with MMLV RT Catalytic Fragment
Overview
A general strategy for the rapid structural analysis of DNA binding ligands is described as it was applied to the study of RT29, a benzimidazole-diamidine compound containing a highly twisted diphenyl ether linkage. By combining the existing high-throughput fluorescent intercalator displacement (HT-FID) assay developed by Boger et al. and a high-resolution (HR) host-guest crystallographic technique, a system was produced that was capable of determining detailed structural information pertaining to RT29-DNA interactions within approximately 3 days. Our application of the HT/HR strategy immediately revealed that RT29 has a preference for 4-base pair (bp), A.T-rich sites (AATT) and a similar tolerance and affinity for three A-T-bp sites (such as ATTC) containing a G.C bp. On the basis of these selectivities, oligonucleotides were designed and the host-guest crystallographic method was used to generate diffraction quality crystals. Analysis of the resulting crystal structures revealed that the diphenyl ether moiety of RT29 undergoes conformational changes that allow it to adopt a crescent shape that now complements the minor groove structure. The presence of a G.C bp in the RT29 binding site of ATTC did not overly perturb its interaction with DNA-the compound adjusted to the nucleobases that were available through water-mediated interactions. Our analyses suggest that the HT/HR strategy may be used to expedite the screening of novel minor groove binding compounds leading to a direct, HR structural determination.
About this Structure
2FJV is a Single protein structure of sequence from Moloney murine leukemia virus. Full crystallographic information is available from OCA.
Reference
A high-throughput, high-resolution strategy for the study of site-selective DNA binding agents: analysis of a "highly twisted" benzimidazole-diamidine., Goodwin KD, Lewis MA, Tanious FA, Tidwell RR, Wilson WD, Georgiadis MM, Long EC, J Am Chem Soc. 2006 Jun 21;128(24):7846-54. PMID:16771498 Page seeded by OCA on Sun May 4 03:58:55 2008
